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VESTIBULAR MODULATION OF THYROID
FUNCTION IN FORCED COLD WATER
SWIMMING STRESS INDUCED Wistar albino
RATS
BY
VARSHA VARGHESE P
Dissertation Submitted to the
Kerala University of Health Sciences, Thrissur
In partial fulfillment
of the requirements for the degree of
MASTERS
In
MEDICAL PHYSIOLOGY
Under the guidance of
G Sai Sailesh Kumar
DEPARTMENT OF PHYSIOLOGY
LITTLE FLOWER INSTITUTE OF MEDICAL
SCIENCES AND RESEARCH
ANGAMALY
2016
KERALA UNIVERSITY OF HEALTH SCIENCES
THRISSUR
DECLARATION BY THE CANDIDATE
I hereby declare that this dissertation entitled “VESTIBULAR MODULATION OF
THYROID FUNCTION IN FORCED COLD WATER SWIMMING STRESS
INDUCED Wistar albino RATS” is a bonafide and genuine research work carried
out by me under the guidance of Mr.G Sai Sailesh Kumar, Head of the
Department, Department of Physiology, LIMSAR, Angamaly.
Date:
VARSHA VARGHESE P
Place:
Reg No: 132860006
COPYRIGHT
Declaration by the Candidate
I hereby declare that the Kerala University of Health Sciences, Thrissur shall have the
rights to preserve, use and disseminate this dissertation/thesis in print or electronic
format for academic/research purpose.
Date:
Place:
VARSHA VARGHESE P
ABSTRACT
OBJECTIVE
The present study was undertaken to provide experimental evidence for vestibular
modulation of thyroid function in cold water swimming stress induced Wistar albino
rats.
MATERIALS AND METHOD
24 healthy, adult male albino rats of Wistar strain were used in the present study. Rats
were forced to swim in the plastic tubs (height: 60 cm, diameter: 40 cm) containing
cold water, maintained at 10°C. Depth of the water in the plastic tub was 30 cm. The
swimming session lasted for 45 minutes daily. The middle ear cavity was irrigated
with hot (40 degree centigrade) or cold (15 degree centigrade) water through a
polyethylene tube for 15 days.
RESULTS
Significant decrease in T3, T4 levels, an increase in cholesterol and body weight was
observed in stress only group, whereas no such changes observed in vestibular
stimulation group.
CONCLUSION
Our study provides preliminary evidence that vestibular stimulation can effectively
prevent stress induced changes in body weight and thyroid hormones secretion. We
recommend translational research in this area to elucidate the mechanism of vestibular
modulation of thyroid hormones secretion.
KEY WORDS: Caloric vestibular stimulation; Cold water swimming stress; Thyroid
hormones.
I
TABLE OF CONTENTS
SL.NO:
CONTENTS
PAGES
1.
INTRODUCTION
1
2.
OBJECTIVE
4
3.
REVIEW OF LITERATURE
6
4.
METHODOLOGY
37
5.
RESULTS
41
6.
DISCUSSION
46
7.
CONCLUSION
50
8.
REFERENCES
52
9.
ANNEXURES
62
II
LIST OF FIGURES
SL.NO:
FIGURES
PAGES
1
Thyroid gland and larynx
7
2
Hypothalamo pituitary thyroid axis.
9
3
Vestibular apparatus
21
4
Typical
hair
cells
(flask
and
cuboid)
23
synapsing with afferent and efferent nerve
5
Change in hair cells with respect to
24
movement
6
Swing- controlled vestibular stimulation
29
7
Sympathetic Adrenal Medullary axes
32
8
Hypothalamo Pituitary Adrenal Axis
34
III
9
Caloric vestibular stimulation
40
10
Body weight before and after vestibular
42
stimulation.
11
T3
levels
before
and
after
vestibular
43
stimulation
T4 levels before and after vestibular
12
44
stimulation
Cholesterol levels before and after vestibular
13
45
stimulation
IV
ANNEXURES
SL.NO:
TITLE
PAGES
Acknowledgement
63
1
2
List of abbreviations used
3
Publications
65
67
V
INTRODUCTION
1
CHAPTER I
INTRODUCTION
Stress is the generalized, non-specific response of the body to any factor that
overwhelms or threatens to overwhelm, the body’s compensatory abilities to maintain
homeostasis. Stress causes physiological changes, biochemical changes and behavioral
changes in our body.1,2 Stress can cause thyroid autoimmunity.3 In laboratory animals
forced swimming is most widely accepted for studying physiological variations in
response to stress. It was reported that rats could survive 80 hours in lukewarm water
(36°C). Increase or decrease in the temperature of water influences the behavior of the
animal and changes the influence of glucocorticoids.4, 5 Stress modulates secretion of
hormones and may lead to endocrine disorders. Stress increases secretion of
Glucocorticoids, growth hormone, prolactin and catecholamines. Increase in these
hormones will help the individual to cope up with the stressful condition. However
stress will decrease secretion of thyroid hormone and insulin. Both T3, T4 levels
decreases in response to stress. Stress inhibits thyroid stimulating hormone through the
action of glucocorticoids on the nervous system.6Stress causes hypothyroid symptoms
by disrupting HPA axis, reduces the conversion of T4 to T3, promote autoimmunity by
weakening immune barriers, causes thyroid hormone resistance and causes hormonal
imbalances.7
Vestibular apparatus is known as membranous labyrinth and is enclosed in bony
labyrinth of temporal bone. Vestibular apparatus consists of otolith organs and three
semi circular canals. Vestibular stimulation relieves stress, pain, promotes sleep,
2
improves cognition, immunity, balance food intake and also treats endocrine
disorders.8-13Vestibular stimulation modulates thyroid hormone secretion through its
connections with paraventricular nucleus and arcuate nucleus.14The present study was
undertaken to provide preliminary experimental evidence for vestibular modulation of
thyroid function in cold water swimming stress induced Wistar albino rats and to
suggest further research to recommend vestibular stimulation as an intervention for
thyroid disorders.
3
OBJECTIVES
4
CHAPTER 2
OBJECTIVES
MAIN OBJECTIVE
To study the Effect of caloric vestibular stimulation on modulation of thyroid function
in cold water swimming stress induced Wistar albino rats.
OTHER OBJECTIVE
To compare the effect of hot and cold water vestibular stimulation on thyroid function.
HYPOTHESIS
Vestibular stimulation may prevent stress induced changes in thyroid function.
5
REVIEW
OF
LITERATURE
6
CHAPTER 3
REVIEW OF LITERATURE
THYROID GLAND IT’S METABOLIC ROLES
Thyroid gland is one of the largest glands (15-20 gms in adult) in endocrine system.
The butter fly shaped gland located immediately below the larynx on each side
anterior to trachea. It has 2 lobes connected by isthmus (figure 1). When the TSH from
the hypothalamus comes, the thyroid follicles become active and secrete 2 hormones,
thyroxin (T4) and triiodothyronine (T3). Parafollicular cells or C cells present in
between follicles which secrete calcitonin, it helps to regulate calcium homeostasis.15
Figure 1: The thyroid gland and larynx 16
7
BIOSYNTHESIS AND STORAGE OF THYROID HORMONES
T3 and T4 are synthesized from tyrosine and iodine by enzyme peroxidase. First step is
uptake of iodine by thyroid. It is an energy requiring process. TSH controls the iodine
uptake and antithyroid agents inhibit iodine transport. Thyrosine residue serves as the
substrate for hormone synthesis and is present in thyroglobulin which is a large
glycoprotein. Next step is the oxidation of iodide. Pendrin is the transporter helps to
move the iodide to apical surface of epithelial cells where it is oxidised to by the
enzyme peroxidase. After that iodination Thyrosine residue of thyroglobulin initially
to monoiodotyrosine (MIT) and then to diiodotyrosine (DIT). Next is coupling
reaction. 2 molecules of DIT couple to form cone molecule of MIT and one molecule
of DIT coupled to form T3 with the help of peroxidase. Iodinated thyroglobulin is
stored in follicle as colloid for several months.30
SECRETION, TRANPORT AND METABOLISM OF THYROID HORMONES
Through endocytosis colloid containing iodinated thyroglobulin is retrieved and by
pinocytosis colloid enters the cytoplasm as colloid droplets. Colloid droplets then fuse
with lysosome vesicles and digest the thyroglobulin molecule releasing T3 ,T4, DIT,
MIT .among them DIT and MIT are rapidly deiodinated and the iodine is reused.
Transport of T3 and T4 either by bound form by thyroxine binding globulin, thyroxine
binding prealbumin and by thyroxine binding albumin or by free form. These free
unbound hormones represent the biologically active hormone.
Metabolism of circulating hormone includes deiodination, deamination and
conjugation. T4 is deiodinated in to T3 and reverse T3 which are then in to DIT and
8
MIT. DIT is further deiodinated to MIT. Very small amount of T3 and T4 undergoes
decarboxylation to form tetraiodothyroaceticacid and triiodothyroacetic acid. Thyroid
hormones are conjugated in liver to form glucuronides and sulphates. Metabolites of
T3 and T4 are mainly excreted through faeces with a small amount in urine.30
REGULATION OF THYROID HORMONE SECRETION
Regulation is mainly by negative feedback mechanism through HPT axis and auto
regulation of thyroid gland (figure 2). TSH from the anterior pituitary regulates the
thyroid hormone secretions. Increased TSH increase all the steps of biosynthesis,
increase the number and size of follicular epithelial cells and increase the vascularity
of thyroid gland. A fall in thyroid hormone stimulates TSH secretion and rise in
thyroid hormone inhibit TSH secretion.
Figure 2: Hypothalamo Pituitary Thyroid axis
9
30
TSH from anterior pituitary is controlled by hypothalamic tyrotropin releasing
hormones (TRH). TRH is secreted by arcuate nucleus of hypothalamus and stored in
median eminence which is released into hypothalamo hypophyseal portal vessels to
reach anterior pituitary. Exposure to cold, emotions, stress and negative control by
plasma T3 and T4 levels will regulate the TRH production from hypothalamus.
Autoregulation is according to the availability iodine content in the food. If
availability is high iodine trapping mechanism is less efficient and if the availability is
minimum iodine trapping mechanism is super efficient.16
FUNCTIONS OF THYROID HORMONES (T3, T4)
Thyroid hormones increase the Transcription of large number of genes along with
steroids and retinoids.17 Most of the T4 secreted by the thyroid is converted to T3.18
Thyroid hormones activate nuclear receptors.19 Thyroid hormones increase cellular
metabolic activity.20 It increase the number and activity of mitochondria.21
It has positive role in growth. It regulate chondrocyte cell growth and differentiation in
the
endochondral
growth
plate.22
Stimulates
carbohydrate
and
fat
metabolism.23.Increased basal metabolic rate.24 Increase in the hormone secretion will
decreases the body weight.25
Patients with thyroid disease, usually has altered cardiac function such as heart rate,
cardiac output, and systemic vascular resistance which are closely related to thyroid
status.26
Thyroid hormones play an important role in CNS especially in maturation phase.
Absence of thyroid hormones produce multiple morphological and biochemical
10
alteration and in humans leads to irreversible mental retardation.27 Thyroid hormones
may either have a direct vasodilating effect or increase shunting in vascular beds of
rats.28
Pregnancy has a profound impact on thyroid gland function, it is a stress test for the
thyroid resulting in hypothyroidism in women with limited thyroid reserve and
postpartum thyroiditis in women with Hashimoto’s disease who were euthyroid prior
to conception.29
Above studies revealed that thyroid hormones involved in almost all functions in our
body. Any change in the level of hormone will alter the vital process in our body.
Under functioning of thyroid is hypothyroidism, over functioning of thyroid is
hyperthyroidism and normal thyroid is euthyroid.
DISEASES OF THE THYROID
1-Hyperthyroidism (over functioning of thyroid)
In most patients with hyperthyroidism, the thyroid gland is increased to two to three
times' normal size, with tremendous hyperplasia and infolding of the follicular cell
lining into the follicles, so the number of cells is increased greatly. Also, each cell
increases its rate of secretion several fold; radioactive iodine uptake studies indicate
that some of these hyperplastic glands secrete thyroid hormone at rates 5 to 15 times
normal. Graves' disease, the most common form of hyperthyroidism, is an
autoimmune disease in which antibodies called thyroid-stimulating immunoglobulins
(TSIs) form against the TSH receptor in the thyroid gland. These antibodies bind with
the same membrane receptors that bind TSH and induce continual activation of the
11
cAMP system of the cells, with resultant development of hyperthyroidism. The TSI
antibodies have a prolonged stimulating effect on the thyroid gland, than TSH. The
high level of thyroid hormone secretion caused by TSI in turn suppresses anterior
pituitary formation of TSH. Therefore, TSH concentrations are less than normal (often
essentially zero) rather than enhanced in almost all patients with Graves' disease.3
2- Thyroid Adenoma
Hyperthyroidism occasionally results from a localized adenoma (a tumor) that
develops in the thyroid tissue and secretes large quantities of thyroid hormone. This is
different from the more usual type of hyperthyroidism in that it is usually not
associated with evidence of any autoimmune disease. An interesting effect of the
adenoma is that as long as it continues to secrete large quantities of thyroid hormone,
secretory function in the remainder of the thyroid gland is almost totally inhibited
because the thyroid hormone from the adenoma depresses the production of TSH by
the pituitary gland.
Symptoms of Hyperthyroidism
The symptoms of hyperthyroidism are a high state of excitability, intolerance to heat,
increased sweating, mild to extreme weight loss (sometimes as much as 100 pounds),
varying degrees of diarrhea, muscle weakness, nervousness or other psychic disorders,
extreme fatigue but inability to sleep, and tremor of the hands.30
3- Exophthalmos
Most people with hyperthyroidism develop some degree of protrusion of the eyeballs.
This condition is called exophthalmos. A major degree of exophthalmos occurs in
12
about one third of hyperthyroid patients, and the condition sometimes becomes so
severe that the eyeball protrusion stretches the optic nerve enough to damage vision.
Much more often, the eyes are damaged because the eyelids do not close completely
when the person blinks or is asleep. As a result, the epithelial surfaces of the eyes
become dry and irritated and often infected, resulting in ulceration of the Cornea. The
cause of the protruding eyes is edematous swelling of the retro-orbital tissues and
degenerative changes in the extraocular muscles. In most patients, immunoglobulins
that react with the eye muscles can be found in the blood. Furthermore, the
concentration of these immunoglobulins is usually highest in patients who have high
concentrations of TSIs. Therefore, there is much reason to believe that exophthalmos,
like hyperthyroidism itself, is an autoimmune process. The exophthalmos is usually
greatly ameliorated with treatment of the hyperthyroidism.
Diagnostic Tests for Hyperthyroidism
For the usual case of hyperthyroidism, the most accurate diagnostic test is direct
measurement
of
the
concentration
of
"free"
thyroxine
(and
sometimes
triiodothyronine) in the plasma, using appropriate radioimmunoassay procedures.
Other tests that are sometimes used are as follows:
- The basal metabolic rate is usually increased to +30 to +60 in severe
hyperthyroidism.
-The concentration of TSH in the plasma is measured by radioimmunoassay. In the
usual type of thyrotoxicosis, anterior pituitary secretion of TSH is so completely
13
suppressed by the large amounts of circulating thyroxine and triiodothyronine that
there is almost no plasma TSH.
- The concentration of TSI is measured by radioimmunoassay. This is usually high in
thyrotoxicosis but low in thyroid adenoma.
Physiology of Treatment in Hyperthyroidism
The most direct treatment for hyperthyroidism is surgical removal of most of the
thyroid gland. In general, it is desirable to prepare the patient for surgical removal of
the gland before the operation. This is done by administering propylthiouracil, usually
for several weeks, until the basal metabolic rate of the patient has returned to normal.
Then, administration of high concentrations of iodides for 1 to 2 weeks immediately
before operation causes the gland itself to recede in size and its blood supply to
diminish. By using these preoperative procedures, the operative mortality is less than 1
in 1000 in the better hospitals, whereas before development of modern procedures,
operative mortality was 1 in 25.
Treatment of the Hyperplastic Thyroid Gland with Radioactive Iodine80 to 90 percent
of an injected dose of iodide is absorbed by the hyperplastic, toxic thyroid gland
within 1 day after injection. If this injected iodine is radioactive, it can destroy most of
the secretory cells of the thyroid gland. Usually 5 mill curies of radioactive iodine is
given to the patient, whose condition is reassessed several weeks later. If the patient is
still hyperthyroid, additional doses are administered until normal thyroid status is
reached.30
14
4- Hypothyroidism
The effects of hypothyroidism, in general, are opposite to those of hyperthyroidism,
but there are a few physiological mechanisms peculiar to hypothyroidism.
Hypothyroidism, like hyperthyroidism, is often initiated by autoimmunity against the
thyroid gland (Hashimoto disease), but immunity that destroys the gland rather than
stimulates it. The thyroid glands of most of these patients first have autoimmune
"thyroiditis,"
which
means
thyroid
inflammation.
This
causes
progressive
deterioration and finally fibrosis of the gland, with resultant diminished or absent
secretion of thyroid hormone. Several other types of hypothyroidism also occur, often
associated with development of enlarged thyroid glands, called thyroid goiter, as
follows.30
5-Thyroid goiter
Endemic Colloid Goiter Caused by Dietary Iodide Deficiency. The term "goiter"
means a greatly enlarged thyroid gland. As pointed out in the discussion of iodine
metabolism, about 50 milligrams of iodine are required each year for the formation of
adequate quantities of thyroid hormone. In certain areas of the world, notably in the
Swiss Alps, the Andes, and the Great Lakes region of the United States, insufficient
iodine is present in the soil for the foodstuffs to contain even this minute quantity.
Therefore, in the days before iodized table salt, many people who lived in these areas
developed extremely large thyroid glands, called endemic goiters. The mechanism for
development of large endemic goiters is the following: Lack of iodine prevents
production of both thyroxine and triiodothyronine. As a result, no hormone is
15
available to inhibit production of TSH by the anterior pituitary; this causes the
pituitary to secrete excessively large quantities of TSH. The TSH then stimulates the
thyroid cells to secrete tremendous amounts of thyroglobulin colloid into the follicles,
and the gland grows larger and larger. But because of lack of iodine, thyroxine and
triiodothyronine production does not occur in the thyroglobulin molecule and
therefore does not cause the normal suppression of TSH production by the anterior
pituitary. The follicles become tremendous in size, and the thyroid gland may increase
to 10 to 20 times' normal size.
Idiopathic Nontoxic Colloid Goiter: Enlarged thyroid glands similar to those of
endemic colloid goiter can also occur in people who do not have iodine deficiency.
These goitrous glands may secrete normal quantities of thyroid hormones, but more
frequently, the secretion of hormone is depressed, as in endemic colloid goiter. The
exact cause of the enlarged thyroid gland in patients with idiopathic colloid goiter is
not known, but most of these patients show signs of mild thyroiditis; therefore, it has
been suggested that the thyroiditis causes slight hypothyroidism, which then leads to
increased TSH secretion and progressive growth of the non inflamed portions of the
gland. This could explain why these glands are usually nodular, with some portions of
the gland growing while other portions are being destroyed by thyroiditis. In some
persons with colloid goiter, the thyroid gland has an abnormality of the enzyme
system required for formation of the thyroid hormones. Among the abnormalities
often encountered are the following:
16
-Deficient iodide-trapping mechanism, in which iodine is not pumped adequately into
the thyroid cells
- Deficient peroxidase system, in which the iodides are not oxidized to the iodine state
-Deficient coupling of iodinated tyrosines in the thyroglobulin molecule so that the
final thyroid hormones cannot be formed
-Deficiency of the deiodinase enzyme, which prevents recovery of iodine from the
iodinated tyrosines that are not coupled to form the thyroid hormones (this is about
two thirds of the iodine), thus leading to iodine deficiency
Finally, some foods contain goitrogenic substances that have a propylthiouracil-type
of antithyroidactivity, thus also leading to TSH-stimulated enlargement of the thyroid
gland. Such goitrogenic substances are found especially in some varieties of turnips
and cabbages.
Physiological Characteristics of Hypothyroidism
Whether hypothyroidism is due to thyroiditis, endemic colloid goiter, idiopathic
colloid goiter, destruction of the thyroid gland by irradiation, or surgical removal of
the thyroid gland, the physiological effects are the same. They include fatigue and
extreme somnolence with sleeping up to 12 to 14 hours a day, extreme muscular
sluggishness, slowed heart rate, decreased cardiac output, decreased blood volume,
sometimes increased body weight, constipation, mental sluggishness, failure of many
trophic functions in the body evidenced by depressed growth of hair and scaliness of
the skin, development of a froglike husky voice, and, in severe cases, development of
an edematous appearance throughout the body called myxedema.
17
6-Myxedema
Myxedema develops in the patient with almost total lack of thyroid hormone function.
Such patient, demonstrating bagginess under the eyes and swelling of the face. In this
condition, for reasons not explained, greatly increased quantities of hyaluronic acid
and chondroitin sulfate bound with protein form excessive tissue gel in the interstitial
spaces and this causes the total quantity of interstitial fluid to increase. Because of the
gel nature of the excess fluid, it is mainly immobile and the edema is the nonpitting
type.30
7-Atherosclerosis in Hypothyroidism
Lack of thyroid hormone increases the quantity of blood cholesterol because of altered
fat and cholesterol metabolism and diminished liver excretion of cholesterol in the
bile. The increase in blood cholesterol is usually associated with increased
atherosclerosis. Therefore, many hypothyroid patients, particularly those with
myxedema, develop atherosclerosis, which in turn results in peripheral vascular
disease, deafness, and coronary artery disease with consequent early death.
Diagnostic Tests in Hypothyroidism
The tests already described for diagnosis of hyperthyroidism give opposite results in
hypothyroidism. The free thyroxine in the blood is low. The basal metabolic rate in
myxedema ranges between -30 and -50. And the secretion of TSH by the anterior
pituitary when a test dose of TRH is administered is usually greatly increased (except
in those rare instances of hypothyroidism caused by depressed response of the
pituitary gland to TRH).
18
Treatment of Hypothyroidism
The effect of thyroxine on the basal metabolic rate, demonstrating that the hormone
normally has duration of action of more than 1 month. Consequently, it is easy to
maintain a steady level of thyroid hormone activity in the body by daily oral ingestion
of a tablet or more containing thyroxine. Furthermore, proper treatment of the
hypothyroid patient results in such complete normality that formerly myxedematous
patients have lived into their 90s after treatment for more than 50 years. 30
8-Cretinism
Cretinism is caused by extreme hypothyroidism during fetal life, infancy, or
childhood. This condition is characterized especially by failure of body growth and by
mental retardation. It results from congenital lack of a thyroid gland (congenital
cretinism), from failure of the thyroid gland to produce thyroid hormone because of a
genetic defect of the gland, or from iodine lack in the diet (endemic cretinism).The
severity of endemic cretinism varies greatly, depending on the amount of iodine in the
diet, and whole populaces of an endemic geographic iodine-deficient soil area have
been known to have cretinoid tendencies. A neonate without a thyroid gland may have
normal appearance and function because it was supplied with some (but usually not
enough) thyroid hormone by the mother while in utero. A few weeks after birth,
however, the neonate's movements become sluggish and both physical and mental
growth begin to be greatly retarded. Treatment of the neonate with cretinism at any
time with adequate iodine or thyroxine usually causes normal return of physical
growth, but unless the cretinism is treated within a few weeks after birth, mental
19
growth remains permanently retarded. This results from retardation of the growth,
branching, and myelination of the neuronal cells of the central nervous system at this
critical time in the normal development of the mental powers. Skeletal growth in the
child with cretinism is characteristically more inhibited than is soft tissue growth. As a
result of this disproportionate rate of growth, the soft tissues are likely to enlarge
excessively, giving the child with cretinism an obese, stocky, and short appearance.
Occasionally the tongue becomes so large in relation to the skeletal growth that it
obstructs swallowing and breathing, inducing a characteristic guttural breathing that
sometimes chokes the child.30
VESTIBULAR APPARATUS
Vestibular system was discovered by a French anatomist, Pierre Flourens. Vestibular
apparatus is known as membranous labyrinth and is enclosed in bony labyrinth of
temporal bone. Vestibular apparatus consists of otolith organs and three semi circular
canals (figure 3). The balance (vestibular) system in the ears develops very early and
begins to function at five months of gestation.10, 11
The semicircular canals, the utricle, and the saccule are all integral parts of the
equilibrium.
SEMICIRCULAR CANALS
In semicircular canals hair cells are located in ampulla. The ampulla opens into utricle.
Each ampulla contains crista terminalis located on pendular hillock. Hair cells are
presented in the crista ampullaris.
20
Figure 3: vestibular apparatus
16
The cilia of ampullary hair cells are embedded in gelatinous mass known as cupula
that forms a water tight space between the canal and the utricle. However it does not
contain otoliths. Thus specific gravity of copular fluid is same as that of endolymph.31
MECHANISM OF ACTION
When head rotates to one side, canals being part of the head automatically rotate to
that side. However endolymph does not move immediately for about 20 sec due to
natural inertia of gelatinous fluid. If head rotates to right, for initial 20 sec endolymph
practically rotate to the left. Cupular fluid having the same specific gravity as that of
endolymph moves along the direction of endolymph. The copular deflection bends the
21
cilia of hair cells. In the ampulla, the kinocilia are located towards the utricle.
Therefore displacement of cupula towards the utricle bends cilia towards kinocilium
and stimulates hair cells. Thus head rotation is detected in the first 20 sec. After the
initial lag period the movement of endolymph equalizes with the movement of canal.
Therefore rotation is not detected after the initial phase.
When head rotation stops endolymph in the canal continues to move in the same
direction of about 20 secs, which causes deflection of cupula away from the utricle
and the hair cells are inhibited. However, arrangement of hair cells in the canal of both
the ears is such that the beginning of rotation is detected by the hair cells in the ear
towards which rotation takes place, and the termination of rotation is detected by the
hair cells in the opposite ear.
HAIR CELL
Macula is a small sensory area of utricle and saccule which sense orientation of
head when the head is upright (utricle) and also when the person in lying down
(saccule) layer. The bases and sides of the hair cells synapse with sensory endings of
the vestibular nerve. Macula is covered by a gelatinous layer which contains
statoconia (calcium carbonate crystals). Thousands of hair cells are present in macula.
Hair cell project cilia up into the gelatinous. Each hair cell has 50 to 70 small cilia
(stereocilia) and one large cilium (kinocilium). The kinocilium is always located to
one side, and the stereocilia become progressively shorter toward the other side of the
cell. Minute filamentous attachments present between these cilia. (Figure 4) Hair cells
of otolith organs are stimulated by linear acceleration.31
22
Figure 4 : Typical hair cells (flask and cuboid) synapsing with afferent and efferent nerve
Thus saccule detects linear acceleration in vertical direction (eg: experiencing
acceleration while using the lift) and utricle detects linear acceleration in horizontal
direction (eg: experiencing acceleration in a car when the car starts moving). They
also detect change in head position like tilting or bending of head.
MECHANISM OF ACTION
Cilia of hair cells are embedded in otolith membrane that contains otoliths. They are
heavier than endolymph. Thus specific gravity of otolith membrane is more than that
of the endolymph. Therefore a change in the direction of gravitational pull exerted on
the otolith membrane bends the cilia of hair cells. Otolith organ detect change in head
position and linear acceleration.
23
Figure 5: Change in hair cells with respect to movement.
37
With change in head position like tilting of head, change occurs in the direction of
gravitational pull exerted on its otolith membrane. This results in gravitational
movement of otolith membrane. (figure 5) As cilia are entrenched in otolith
membrane, head tilt bends cilia of some
During linear acceleration, due to higher specific gravity of otolith membrane, the
membrane lags behind because of greater inertia imparted to it than the endolymph.
This causes bending of cilia that are embedded in the otolith membrane. Thus action
potential frequency in eighth nerve increases.
24
VESTIBULAR PATHWAYS
Vestibular informations are conveyed to CNS via vestibular division of eighth cranial
nerve. The cell bodies of afferent fibers are located in the scarpa’s ganglion (vestibular
ganglion). They are bipolar neurons. The central axons travel in eighth cranial nerve
which enters the brain at the level of Pons and terminating vestibular nuclei in the
brain stem. There are four nuclei: lateral, medial, superior and inferior.31
1. Lateral vestibular nucleus: this receives fibers from utricle, cerebellum and spinal
cord. Efferent fibers from lateral vestibulospinal tract that facilitate extensor
group of motor neurons supplying antigravity muscles.
2. Medial and superior vestibular nuclei: these two nuclei receive fibers from otolith
organs, semicircular canal and cerebellum. Efferent fibers medial nucleus form
medial vestibulospinal tract. Fibres from superior nucleus project to the
vestibulocerebellum and occulomotor nerve nucleus.
3. Inferior vestibular nucleus: it receives fibers from cerebellum and project to the
cervical spinal cord.
Thus, vestibular apparatus conveys information to three major structures- cerebellum,
occulomotor nuclei and spinal cord motor neurons.
Through cerebellar connections it maintains equilibrium and coordinates postural
movements. Through occulomotor nucleus it regulate eye movements coordinate with
bodily movements. Through spinal motor neurons it controls postural reflexes. By
controlling postural muscles of head and neck vestibular apparatus maintain postural
stability during movement.31
25
VESTIBULAR STIMULATION
The need for vestibular stimulation can be observed throughout the life.9
vestibular stimulation system is the stimulation element that performs the actual
stimulation of the vestibular tissue, a sensor to detect a physiological condition of the
patient, and a power/control unit that receives the signals provided by the sensor and
causes stimulation energy to be provided to the stimulation element at an appropriate
timing, level, pattern, and/or frequency to achieve the desired function.32
The selection of stimulation must be suitable for the subject to achieving the desired
physiological function.
TECHNIQUES OF VESTIBULAR STIMULATION
* Electrical Stimulation— in this electrically conductive electrodes in, on, and/or
near the tissue to be stimulated so that an electric current can be delivered to the
adjacent tissue via the electrode. The electrode or electrodes can have a variety of
sizes and configurations depending on the stimulation pattern to be provided. For
example, a point electrode can be used to stimulate a very specific site, or a spot or
strip electrode can be provided to induce stimulation over a larger area.
Eg. Galvanic vestibular stimulation – in these two electrodes placed over the mastoid
process, stimulates and/or inhibits all peripheral vestibular afferents of both the
semicircular canals and the otoliths. 33
*Mechanical Stimulation— In this pressure application device is used. eg, inflatable
balloon. It place near the tissue to be stimulated so that inflating the balloon applies a
pressure on the adjacent tissue. This type of mechanical stimulation system provides
26
pressure fluctuations to the subject to promote a particular sensation. Another example
is a pressure cuff, which is placed either completely or partially around the canal or
nerve to be stimulated so that inflating the pressure cuff exerts pressure on the
underlying portion of the semicircular canal or nerve. Yet another mechanical
stimulation device is a vibrating element that produces a mechanical vibration at a
selected frequency.
*Sonic Stimulation— In this, stimulating the vestibular area or specific sites within
this area using a sonic or ultrasonic device that delivers stimulation on a carrier wave
typically above 20,000 Hz, which is not in the audible range for humans.
* Magnetic Stimulation— In this a magnetic field generator in the form of one or
more coils in and/or near the inner ear. The coils generate a time varying magnetic
field that created a spatially varying electric field that induces stimulation in the target
tissue.
*Chemical Stimulation— In this introduces chemicals causes chemical reactions at a
stimulation site to control the stimulation at that site. For example, an injection or
medicine pump can be provided at the inner ear to introduce the desired stimulation
medication at the stimulation site.
*Radio-Frequency Stimulation— In this using radio frequency wavelengths
generated by a suitable device to provide the desired stimulation. For example, power
and control data using radio frequencies (rf) received by one or more micro
stimulators implanted in the subject. Different micro stimulators implanted at different
27
locations in the patient can be tuned to different frequencies so that a wide variety of
stimulation patterns can be achieved.
*Infrared Stimulation— In this using infrared technology to deliver the stimulation
to the patient's tissues. Short wave, 7,200-15,000Å, or long wave, 15,000-150,000Å,
systems can be used to deliver the stimulation to the target site.32
*Motion Devices – It includes conventional swings, hanging bed, rotational chair,
cradles etc.33
o Rotational Movement by Barany Chair- the subject is made sit in the chair with
head tilted forward at 300. The chair rotated at 30rpm for 20s. During rotation
with eyes open, nystagmus occurs continuously throughout the period of rotation.
After rotation in Barany’s chair for 20s at 30rpm, following effects are noted:

Post rotational nystagmus occurs for 30s.

Dizziness it is associated with feeling of rotation in the opposite
direction.

Vertigo i.e. feeling of rotation in even after stoppage of rotation.

Nausea and vomiting may occur after rotation for a longer period. 16
*Caloric stimulation is performed by irrigating cold and warm water into the ear
canals. This is done one ear at a time. The water stimulates the nerves of the inner ear.
It is according to Barany’s principle. This changes the temperature of the inner ear
and decrease specific gravity and causes rapid, side-to-side eye movements
called nystagmus.31 Here we practiced caloric vestibular stimulation.
28
o
Swing on a swing is a standardised, cheap, comfortable and effective method for
vestibular stimulation. In this method, the participants swing on a swing,
according to their comfort. (Back to front direction).( Figure 6).9
223.52 cm
Observer
Observer
Observer
200.66cm
Observer
200.66cm
Observer
238.76 cm
Figure 6 : Swing- controlled vestibular stimulation9-13
Recent studies shows that vestibular stimulation had a potent soothing effect in
infants, their crying time was decreased.33
Following vestibular stimulation hippocampus, retrosplenial cortex and subiculum
were activated in humans; it is due to spacial disorientation and self rotation
experienced by the subjects during vestibular stimulation.34
29
Caloric vestibular stimulation in humans shows wide spread cortical network and also
right hemispheric dominance of vestibular cortex areas regardless of side of
stimulation.35Galvanic vestibular stimulation helps in figure copying ability in right
hemi sphere stroke individual and there by uncovering the vestibular information
processing and visual task performance.36
STRESS
Stress is defined as a state of disharmony or threatened homeostasis. Stress was coined
by Hens Seyle. The concept of stress and homeostasis can be traced back to ancient
Greek history, however, the integration of these notions with related physiologic and
pathophysiologic mechanism and their association with specific illnesses is much
more recent.54
Stress is the generalized, non-specific response of the body to any factor that
overwhelms or threatens to overwhelm, the body’s compensatory abilities to maintain
homeostasis. Stress causes physiological changes, biochemical changes and behavioral
changes in our body.1,2
A stressor is any person or situation that produces anxiety responses. Stress and
stressors are different for each person. Environmental stressors include noise,
pollution, traffic, crowding and weather. Physiological stressors include illness,
injuries, hormonal fluctuation, inadequate sleep or nutrition. Social stressors include
financial problems, work demands, social events, losing a loved one, exams, interview
and some thoughts like negative self talk, catastrophe and perfectionism are also cause
stress.
30
GENERAL ADAPTATION SYNDROME
Homeostatic mechanisms are aimed at counteracting the everyday stress of living. If
they are successful, the internal environment maintains normal physiological limits of
temperature, chemistry and pressure. If stress is extreme or long lasting the normal
mechanisms may not be sufficient. In this case, the stress triggers a wide ranging set of
bodily changes called the General Adaptation Syndrome (GAS).
When stress appears, it stimulates the hypothalamus to initiate the GAS through two
pathways:
-
First pathway is stimulation of the sympathetic division of the automatic nervous
system and adrenal medulla (sympathetic adrenal medullary axis- SAM axis).
This produces an immediate set of responses called alarm reaction.
-
The second pathway, called the resistance reaction involves the anterior pituitary
gland and adrenal cortex (HPA axis); the resistance reaction is slower to start but
its effect last longer.
SAM axis
It is body’s initial reaction to a stressor. It is a set of reactions initiated when
hypothalamus stimulates the sympathetic division of the autonomic nervous system,
and the adrenal medulla. The alarm reaction is meant to counteract a danger by
mobilizing the body’s resources for immediate physical activity. The reactions
include-Heart rate and strength of cardiac muscle contraction increases; this circulates blood
quickly to areas where it is needed to fight the stress.
31
STRESSORS
STIMULATE
HYPOTHALAMUS
STIMULATE
SYMPATHETIC NERVOUS SYSTEM
STIMULATE
ADRENAL MEDULLA
RELEASE
CATECHOLAMINES (EPINEPHRINE, NOR EPINEPHRINE)
FIGHT/FLIGHT RESPONSE
Figure: 7 Sympathetic Adrenal Medullary axes
-Blood vessels that supply to the skin and viscera, except heart and lungs constrict; at
the same time blood vessels supplying to the skeletal muscles and brain dilate; these
responses route more blood to organs active in the stress responses, thus decreasing
blood supply to organs which do not assume an immediate active role.
-RBC production is increased leading to an increase in the ability of the blood to clot.
This helps control bleeding.
-Liver converts glycogen in to glucose and releases it into the blood stream; this
provides the energy needed to fight the stressor
-The rate of breathing increases and respiratory passages widen to accommodate more
air; this enables the body to acquire more oxygen.
32
- Production of saliva and digestive enzymes reduces. This reaction takes place as
digestive activity is not essential for counteracting stress.
HPA axis
HPA mediated resistance reaction is the second stage in the stress response. It is
initiated by regulating hormones secreted by the hypothalamus, and is long term
reaction. These regulating hormones are corticotrophin releasing hormone (CRH),
growth hormone releasing hormone (GHRH) and thyrotrophic releasing hormone
(TRH).
CRH stimulates the anterior pituitary to increase the secretion of adrenocorticotropic
hormone (ACTH). ACTH stimulates the adrenal cortex to secrete more of its
hormones. The action of these hormones helps to control bleeding, maintain blood
pressure etc.
GHRH stimulates anterior pituitary to secrete human growth hormone (HGH). TRH
causes the anterior pituitary to secrete thyroid stimulating hormone (TSH). The
combined action of HGH and TSH helps to supply additional energy to the body.
The resistance reaction allows the body to continue fighting a stressor for a long time.
Thus it helps us to meet emotional crisis, perform sternus tasks, fighting infection or
resist the threat of bleeding to death.
Generally, the resistance reaction is successful in helping us cope with a stressful
situation, and our bodies then return to normal. Occasionally it fails to fight the
stressor, especially if it is too severe or long lasting. In this case, GAS moves into the
stage of exhaustion.38
33
STRESS
HYPOTHALAMUS
CRH,TRH,GHRH
ANTERIOR PITUITARY
ACTH
TSH
HGH
ADRENAL CORTEX
THYROID GLAND
LIVER
ADRENAL HORMONES
(GLUCOCORTICOIDS,
MINERALOCORTICOIDS)
SUPPLIES ENERGY
THROUGH INCREASED
BREAKDOWN OF
CARBOHDRATES
SUPPLIES ENERGY THROUGH
GLYCONEOGENESIS AND
INCREASED BREAKDOWN OF
FATS
Figure: 8 Hypothalamo Pituitary Adrenal Axis (ACTH-adrenocorticotropic hormone, HGHhuman growth hormone, TSH- thyroid stimulating hormone)
INTERACTION OF STRESS AND THYROID HORMONES
Stress will produce neurohumoral changes especially in hypothalamo-pituitary-adrenal
axis and early stress and maltreatment leads to the emergence of psychiatric disorders
during development.39 stress will stimulate the HPA axis and increase the production
of corticosteroids and vestibular stimulation will relieves stress related changes in
HPA axis. 40,10
Anxiety patients with poor adaptation to vestibular lesion are parallel to quality and
quantity of stress.41Evidence indicating that stressful conditions causes adaptation in
thyroid functions, initial change observed in serum protein bound iodine levels comes
similar to the initial level following intervention.42
34
Cortisol have an inhibitory effect on neurons in the PVN of hypothalamus through
depression of the noradrenergic system in rats.43Stress causes hypothyroid symptoms
by disrupting HPA axis, reduces the conversion of T4 to T3, promote autoimmunity by
weakening immune barriers, causes thyroid hormone resistance and causes hormonal
imbalances.
The impact of cold mild stress will reduce the T3 and T4 levels, these altered thyroid
function in turn alter the immunity.44During stress Corticotrophin-releasing hormone
suppress the thyroid function by inhibiting the secretion of thyroid releasing hormone
and thyroid stimulating hormone.45
Prenatal stress in pregnant female rats, the fetuses exhibit altered somatotopic and
endocrine activities due to alteration in HPA axis.46
INTERACTION BETWEEN THYROID FUNCTION AND VESTIBULAR
SYSTEM
The interaction between the endocrine system and the vestibular system is mainly
unexplored.41 But vestibular stimulation is considered as a supplementary treatment
for hypothyroidism.13
Tyrotropin releasing hormone from the hypothalamus plays key role in the regulation
of thyroid secretions.
Medial vestibular nucleus receives direct connections from hypocretin (orexin)
neurons of lateral hypothalamus.47
Thyroid deficiency may cause vestibulopathy to central vestibular disorders affecting
cerebellum.48
35
Studies shows that caloric vestibular stimulation causes changes in neuronal activity
both inhibition and excitation of paraventricular nucleus in guinea pig.49 Caloric
stimulation of endolymph in guinea pig traced the direct connections between
vestibular
nucleus
and
supraoptic
nucleus
and
paraventricle
nucleus
of
hypothalamus.50 During starvation exogenous supplement of leptin blunts the changes
in thyroid axis in male mice.51 Leptin stimulate TRH biosynthesis7 folds, in addition
of alpha-melanocyte-stimulating hormone (3.5-fold increase in TRH), whereas
neuropeptide Y suppress pro-TRH biosynthesis (3-fold) and melanocortin-4 receptor
antagonist SHU9119 partially inhibited leptin-stimulated TRH release from the
neuronal culture of fetal rat hypothalamus.52
NPY plays major role in controlling HPT axis, when administering NPY in blood it
will cause suppression of thyroid hormone and stable or low level in TSH. 53
Vestibular stimulation suppresses the stress induced changes on thyroid function,
directly through HPT axis and indirectly through the stress axis.65
36
RESEARCH
METHODOLOGY
37
CHAPTER 4
RESEARCH METHODOLOGY
RESEARCH APPROACH
It is an experimental study to test the hypothesis that vestibular stimulation may
prevent stress induced changes in thyroid function. The study was conducted between
November 2014 – February 2015.
VARIABLES
Independent variable – caloric vestibular stimulation
Dependent variables – T3, T4, cholesterol, body weight
SETTING OF THE STUDY
The study was conducted at Department of Physiology, Little Flower Institute of
Medical science and Research Centre, Angamaly, Kerala.
ETHICAL CONSIDERATION
The present study was approved by institutional animal ethical committee of Little
Flower Hospital and Research Centre, Angamaly, No EC/5.
MATERIALS AND METHODS
Animals: 24 healthy, adult male albino rats of Wistar strain with body weight ranging
50-125 gms, were used in the present study. All Rats were housed in polypropylene
cages (30x22x14cm), fed with standard rat-chow and water ad-libitum.
Rats were randomly assigned into four groups, following inclusion and exclusion
criteria.
38
Group A: (n=6) Control Group (Neither stress nor vestibular stimulation)
Group B: (n=6) Stress Group (Cold water swimming stress was given for 15 days)
Group C: (n=6) Cold water swimming stress + cold water vestibular stimulation.(15
days)
Group
D:
(n=6)
Cold
water
swimming
stress+
hot
water
vestibular
stimulation.(15days)
1. Inclusion criteria

Healthy adult rats

Male rats
2. Exclusion criteria

Female rats

Unhealthy diseased rats
METHODS
Cold water swimming stress: Rats were forced to swim in the plastic tubs (height: 60
cm, diameter: 40 cm) containing cold water, maintained at 10°C. Depth of the water in
the plastic tub was 30 cm. The swimming session lasted for 45 minutes daily.
Experiments were done between 9 AM and 12 Noon to minimize the circadian
variability.
Caloric vestibular stimulation: The middle ear cavity was irrigated with hot (40
degree centigrade) or cold (15degree centigrade) water through a polyethylene tube
for15 days.( Figure 8)
39
Figure 9: caloric vestibular stimulation
After recording the baseline values of T3, T4 and cholesterol, Group B,C,D rats were
exposed to cold water swimming stress for 15days. Cold and hot water (caloric)
vestibular stimulation was administered along with cold water swimming stress to
group C, D rats respectively. After values were collected on 7th day and 15th day to
evaluate the effect of vestibular stimulation on prevention of stress induced changes in
thyroid hormone secretion.
T3 and T4 are estimated by using semi luminescent immune assay used for humans but
TSH is not equalent to humans.64 Cholesterol estimation was performed by CHOD
PAP (cholesterol oxidase- phenol + aminophenasone) method.
ANALYSIS AND INTERPRETATION
Data was analyzed by SPSS 20.0. Statistical tests used are Two-way ANOVA and
Bonferroni post tests. P value ˂ 0.05 was considered as significant.
40
RESULTS
41
CHAPTER 5
RESULTS
BODY WEIGHT:
Body weight increased significantly followed by forced cold water swimming stress in
stress only group on 7th day and 15th day. However no significant change was
observed in body weight in cold and hot water vestibular stimulation groups. (Figure
10)
Figure 10: Body weight before and after vestibular stimulation (g-gms)
42
T3 LEVELS:
T3 Levels decreased significantly in stress only group on 7th day followed by forced
cold water swimming stress then comes to normal. However no significant change was
observed in T3 Levels in cold and hot water vestibular stimulation groups. (Figure 11)
Figure 11: T3 levels ( ng/dl ) before and after vestibular stimulation
43
T4 LEVELS :
T4 Levels decreased significantly in stress only group on 7th day followed by forced
cold water swimming stress then comes to normal. However no significant change was
observed in T4 Levels in cold and hot water vestibular stimulation groups.(Figure 12)
Figure 12: T4 levels ( ng/dl ) before and after vestibular stimulation
44
SERUM CHOLESTEROL:
Cholesterol levels increased significantly followed by forced cold water swimming
stress in stress only group on 1st , 7th and 15th days. However no significant change
was observed in cholesterol levels in cold and hot water vestibular stimulation groups.
(Figure 13)
Figure 13: Cholesterol levels before and after vestibular stimulation
45
DISCUSSION
46
CHAPTER 6
DISCUSSION
Stress is what everybody experiences in daily life.Stress causes physiological,
biochemical and behavioral changes in our body. Stress at work is a relatively new
phenomenon of modern lifestyles. It covers all professions, starting from a daily
wages employ to employer, artist to a surgeon, patient to hospital staff. Any change in
the environment demands some coping; and little stress helps us adapt. But, beyond
some point stress becomes distress basically individual’s response to fight/flight a
situation. Stress when pathological, causes lot of physical and mental health
problems.54
It was reported that body weight decreases significantly followed by cold water
swimming stress,13 in contrast it was also reported that chronic stress will results in
obesity and metabolic disorders.55 Oliver and Wardle in their study in college
students’ observed thathealthy eating is related to stress, some eat much more, and
some eat much less than usual.56 Studies also reported that stressed female students
eat more fast foods, snacks, beverages than others.57 In the present study, we have
observed increase in the body weight followed by cold water swimming stress. This
stress induced change in the body weight was not observed in hot and cold water
vestibular stimulation groups. This may be due to vestibular balance of food intake
through vagal stimulation, insulin, arcuate nucleus, HPA axis through thyroid
hormones by promoting sleep.8
47
It was reported that long term exposure to cold decreases T3 and T4 levels.16 We
agree with these results as we have observed decrease in the T3 and T4 levels
followed by forced cold water swimming stress. Evidence indicating that stressful
conditions causes adaptation in thyroid functions, initial change observed in serum
protein bound iodine levels comes similar to the initial level following intervention.42
Short time exposures to cold air do not cause any changes in serum levels of thyroid
hormones or TSH. Long-term exposures to cold air speed up the consumption of
thyroid hormones. It firstly manifests as low levels of free T3 and free T4.58 Recent
studies shows that, mood disturbances are very common in humans working in
Antarctica, their serum free T3 levels were found to be low59 and supplementation
with T4 was found to improve cognitive performance.60 Hence changes in thyroid
function in stress is inevitable. Vestibular stimulation can suppresses the stress
induced thyroid changes directly through the HPT axis and indirectly through the
stress axis.65 In the present study, stress induced changes in thyroid hormones are
prevented by both hot and cold water vestibular stimulation. This may be due to
inhibition of stress axes by vestibular stimulation.
It was reported that total serum cholesterol decreased in response to forced
cold water swimming stress.13 G.H Werstuck, S. R Lents et al., reported that,
homocystein induced endoplasmic reticular stress results in increased hepatic
biosynthesis and uptake of cholesterol and triglycerides.61 An increase in cholesterol
levels were observed in toads maintained in cold water (200C).62 Similar results to the
current data have been reported previously that, an enhancement is observed in mice
48
following stress induction.63 Our study results are in accordance with earlier reports as
we have observed an increase in cholesterol levels following exposure to stress.
However vestibular stimulation by hot and cold water effectively prevented this stress
induced rise in cholesterol levels. This may be due to suppression of stress axes which
in turn control the stress induced decrease in thyroid hormone that takes part in lipid
metabolism. Vestibular stimulation also increases the leptin and decease the ghrelin
production that controls satiety centre and regulates food intake.8
LIMITATIONS AND RECOMMENDATIONS OF THE STUDY
Only male rats were included in the present study. We recommend further detailed
study by including more biomarkers and also including both the genders.
49
CONCLUSION
50
CHAPTER 7
CONCLUSION
Our study provides preliminary evidence for prevention of stress induced changes in
thyroid secretion and body weight by vestibular stimulation. We recommend
translational research in this area to elucidate the mechanism of vestibular modulation
of thyroid hormones secretion to recommend vestibular stimulation in the
management of stress and thyroid disorders.
51
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52
CHAPTER 8
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61
ANEXURES
62
ACKNOWLEDGEMENT
I remember with gratitude and owe my success to the God Almighty for having given
me strength and courage to overcome the difficulties and complete this dissertation
successfully.
I express my deep sense of gratitude to my guide, Mr. SAI SAILESH KUMAR,
Head of the Department of Physiology, LIMSAR, Angamaly, who laid a strong
foundation in moulding this research study and devoted his valuable hours in solving
my doubts, constructive guidance, corrections in time and support in various stages of
study and also he is the one who motivated me to publish my work in a reputed
journal.
I am deeply obliged to Dr. J K. MUKKADAN, Professor and Research Director,
LFMRC for his support and suggestions for the successful completion of the study.
I express my sincere gratitude to Rev. Fr.(Dr).GEORGE M.D, Principal, LIMSAR
Angamaly, for giving the opportunity to utilize all facilities in this reputed institution
for the successful completion of this dissertation.
I extend my sincere gratitude to Rev. Fr. BAIJU KANNAMPILLY, for his
motivating suggestions for proceeding my work.
I would like to acknowledge Mr. POLY P V and Mrs. THRESSIAMMA PETER,
Animal House Assistants, LIMSAR, Angamaly, who have helped in caring and
handling the animals.
I am highly indebted to Wistar albino rats which sacrificed its lives for the completion
of my thesis work successfully.
63
On a personal note, I extend my hearty thanks to my husband Mr. ANTU MAVELY,
my parents Mr. VARGHESE P J and Mrs.
MOLY VARGHESE for their
continued and unfailing love, support, encouragement to overcome the tides of heavy
schedule and problems in the path of progress in the study. I appreciate my baby, my
little girl JEWEL REETHA for abiding my ignorance and patience she showed
during my project work.
I am indebted to my Classmates for their constant support, concern and help to make
this attempt an interesting one.
DATE
VARSHA VARGHESE P
PLACE
64
LIST OF ABBREVATIONS USED
1. ACTH
Adrenocorticotropic Hormone
2. ANOVA
Analysis Of Variants
3. Camp
Cyclic Adenosine Mono Phosphate
4. CHOD PAP
Cholesterol Oxidase phenol Aminophenasone
5. CNS
Central Nervous System
6. CRH
Cortico Tropic Releasing Hormone
7. DIT
DiiodoThyrosine
8. GAS
General Adaptation Syndrome
9. GHRH
Growth Hormone Releasing Hormone
10. HGH
Human Growth Hormone
11. HPA
Hypothalamo Pituitary Adrenal axis
12. HPT
Hypothalamo Pituitary Thyroid axis
13. MIT
MonoiodoThyrosine
14. NPY
Neuropeptide Y
15. PVN
Paraventricle Nucleus
16. RBC
Red Blood Corpuscles
17. SAM
Sympathetic Adrenal Medullary Axis
65
18. SPSS
Statistical Package for the Social Sciences
19. T3
Triiodothyronine
20. T4
Thyroxine
21. TRH
Thyroid releasing Hormone
22. TSH
Thyroid stimulating Hormone
23. TSI
Thyroid Stimulating Immunoglobulins
66
PUBLICATIONS
 Varsha VP, Kumar SS, Archana R, Mukkadan JK.
Vestibular modulation of thyroid function in forced cold
water swimming stress induced wistar albino rats. IJRAP.
2014;6(4):513-5.
 Mukkadan J K, Archana R, Kumar SS, Varsha VP, Arati A,
Reddy UK et al. Stress, thyroid hormone secretion and
vestibular stimulation: A review of links. BEMS report.
2015;1(2) :31-34.
67