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Effects of Noopept on Alzheimer’s Symptoms 1
Effects of Noopept on Alzheimer’s Symptoms
By Emilie Koetter
Effects of Noopept on Alzheimer’s Symptoms 2
Introduction
Alzheimer’s disease, a progressive form of dementia, causes a decline in mental ability
which includes memory, thinking, perception, language, and can even affect personality. The
exact cause of Alzheimer’s disease is not yet known, but studies have shown that an array of
events occurring in the brain over a vast period of time lead to its evolution. The main precursor
leading to Alzheimer’s disease is the aggregation of Amyloid Beta protein (ABeta peptide)
which forms senile plaques and neurofibrillary tangles in brain tissue. Senile plaques and
neurofibrillary tangles are thought to cause cholinergic deficit which results in memory
deterioration indicative of Alzheimer’s Disease (Ostrovskaya et. al, 2006).
Alzheimer’s is the sixth leading cause of death in the United States and currently has no
known cure, method of prevention, or way to slow its progression (Ostrovskaya et. al, 2006). In
Georgia alone nearly 120,000 people over the age of 65 have been diagnosed with Alzheimer’s
disease. Many studies have explored the possible effects of a class of nutrient-based cognitive
enhancers called nootropics on mental ability and memory-retention in Alzheimer’s patients.
Nootropics can be found as supplements, drugs, functional foods, and nutraceuticals. Interest in
the effects of cognitive enhancers, especially nootropics, has recently increased dramatically due
to their memory enhancing and neuroprotective properties (Ostrovskaya et. al, 2006). My interest
in this topic stems from a desire to preventing onset of Alzheimer’s in family members who are
at high risk for developing this disease.
My primary source is by Ostrovskaya et. al and focuses on improvement of cognitive
function in mice with Alzheimer-like symptoms and hypothesizes that these agents will improve
spatial memory and enhance immune response to prefibril bodies. The primary focus of this
paper is to evaluate the effectiveness of the nootropic noopept (N-phenylacetyl-L-prolylglycine
Effects of Noopept on Alzheimer’s Symptoms 3
ethyl ester) on improving Alzheimer’s symptoms (Ostrovskaya et. al, 2006). Considering the
available research, I hypothesize that noopept may be a gateway to finding a suitable treatment
for the cognitive deficits associated with neurodegenerative diseases, specifically Alzheimer’s
disease.
Methods
Two groups consisting of sixteen male NMRI (National Medical Research Institute) mice
per group were designated for experimentation. Chosen mice fit a specific weight and age for
standardization. This mouse strain was chosen because it exhibits similar immunosuppression to
that found in Alzheimer’s patients. Olfactory bulbectomy operations were performed on one
group of mice which was designated OB (olfactory bulbectomy). Removal of the olfactory bulbs
in mice has been shown to produce Alzheimer-like behavior as well as biochemical and
physiological similarities in the brain. Mice in the second group underwent sham operations and
were designated SO (sham operated). The sham operation consisted of drilling a 2 mm hole
above the olfactory bulbs without removal of the structures (Ostrovskaya et. al, 2006).
After surgery, each group was randomly divided into two additional subgroups. One OB
and one SO subgroup received 0.01mg/kg noopept (NP) per day for 21 consecutive days
(OB+NP and SO+NP). The remaining groups were administered 0.9% saline for 21 days
(OB+saline and SO+saline). Simultaneous to beginning treatment the mice also began training in
a Morris Water Maze created to teach and assess spatial orientation and memory. The maze was
divided into four quadrants and contained an underwater platform in quadrant 3 for the duration
of training. The tank was filled with water which was clouded by powdered milk to make the
platform invisible to the swimming mice (Ostrovskaya et. al, 2006).
Effects of Noopept on Alzheimer’s Symptoms 4
Upon training completion each mouse was tested on learning ability and spatial memory.
Learning ability was measured based on the amount of time taken to reach the platform. After
removing the platform from the tank a separate test was administered to evaluate spatial
memory. Determinants included the amount of time spent in each quadrant and the number of
times each quadrant was entered (Ostrovskaya et. al, 2006).
A link has been determined between amyloid structure aggregates in the brain and the
onset of Alzheimer’s disease. Another goal of this study is to analyze the immunity response to
ABeta peptide, equine lysozyme, and S100b. ABeta peptide was synthesized by the Yu. A.
Ovchinnikov Institute of Bioorganic Chemistry RAS for use in this study (Ostrovskaya et. al,
2006). Equine lysozyme is a calcium-binding protein generally found throughout the human
body and functions as a protein precursor to C-type lysozyme. In Alzheimer’s patients, cerebral
serous fluid is devoid of equine lysozyme (Casaite et. al, 2009). This protein was purchased from
Sigma, USA to be used in this study. S100b is also a calcium-binding protein implicated in
neurodegenerative diseases. S100b is involved in regulation of neuronal survival. S100b is
produced by astrocytes in the central nervous system and is found at higher levels when damage
has occurred in the nervous system (Hauschild et. al, 1999).
Immunity to amyloid structures was determined based on the level of antibodies to ABeta
peptide, equine lysozyme, and S100b in the blood serum using solid phase ELISA (enzymelinked immunosorbent assay). ELISA is an experimental method used to determine the presence
of a substance within a liquid sample. A Student’s t-test was employed to evaluate ELISA results
for immunity while ANOVA (analysis of variance) was used to determine the variation in means
for spatial memory and orientation testing. ANOVA also utilizes the t-test. P values were then
used to evaluate significance of data for each group (Ostrovskaya et. al, 2006).
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Results
All groups displayed a decrease in the time taken to locate the hidden platform during
training (p=0.000001). No difference in the rate of learning was found between groups.
When the hidden platform was removed from the maze during spatial memory testing, a
significant correlation was found between group and quadrant. This correlation was indicated by
both criterion, quadrant occupancy time and the number of entries into each quadrant. Each
group searched for the hidden platform except for OB+saline. OB+saline showed no preference
for any quadrant. The remaining groups (OB+NP, SO+NP, and SO+saline) showed a preference
for quadrant 3 which contained the target platform during training. Both OB+NP and SO+NP
groups showed higher occupancy times in quadrant 3 compared to both groups treated with
saline, as well as a higher number of entries into quadrant 3. These result indicate impaired
spatial memory in OB+saline mice following olfactory bulbectomy and an increase in
consistency following treatment of noopept (Ostrovskaya et. al, 2006).
This study also evaluated the immunity of NMRI mice to ABeta peptide, equine
lysozyme, and S100b. ELISA was employed to measure the autoimmune response to ABeta
peptide. SO and OB mice treated with saline had low levels of antibodies to ABeta structures,
equine lysozyme, and S100b. OB mice treated with noopept had doubled antibody levels to
ABeta peptide, but had no difference in antibodies for equine lysozyme or S100b. The effect of
noopept on SO+NP mice was even greater. Antibody levels for ABeta peptide increased five
times the normal level, but no effect was observed in equine lysozyme or S100b antibody levels
(Ostrovskaya et. al, 2006).
Discussion
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As determined previously and confirmed by this study, olfactory bulbectomy in NMRI
mice results in Alzheimer-like symptoms and behavior. OB mice display impaired cognitive
function, including decreased spatial memory and suppressed immunity to amyloid proteins.
Noopept, administered daily to olfactory bulbectomized mice, restores spatial memory and
increases ABeta peptide antibody levels (Ostrovskaya et. al, 2006).
Preference for quadrant 3 (the quadrant containing the hidden platform during training)
and a significant number of entries into this quadrant indicates restored spatial memory. These
improvements are comparable to normal spatial memory and antibody levels in SO mice treated
with saline. Treatment with noopept does no affect antibody levels to equine lysozyme or S100b
protein. This study proposes that a lack of immunity toward S100b may be the result of
previously existing immune suppression in NMRI mice (Ostrovskaya et. al, 2006).
Two additional studies by Ostrovskaya et. al evaluate additional properties of the
nootropic noopept. The first focuses on the effects of noopept on expression of neurotrophins
NGF (nerve growth factor) and BDNF (brain-derived growth factor) in rat hippocampus.
Neurotrophins play a crucial role in cognitive function, most importantly in both short-term and
long-term memory integration. Deficiency of neurotrophins has been linked to cognitive
impairment in Alzheimer’s disease and many other neurodegenerative diseases. This study
discovered that long-term administration of noopept does not result in increased tolerance, but
continues intensifying NGF and BDNF synthesis. Therefore, by increasing expression of
neurotrophins NGF and BDNF noopept is directly associated with the restoration of damaged
neurons. This study concludes that in addition to the restorative properties of noopept, new
evidence shows that it may also be an efficient preventative therapy when administered at the
onset of Alzheimer’s disease (Ostrovskaya et. al, 2008).
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A second study evaluates the immunological and neuroprotective effects of noopept in
rats. Rats in this study were injected with amyloid beta (ABeta peptide) to simulate long-term
memory impairment characteristic of Alzheimer’s disease. Mild cognitive impairment was
normalized by treatment with noopept. A significant increase in antibodies to ABeta peptide was
also observed. The most distinct discovery of this study is the cholinopositive effect exhibited by
noopept. Previous research has determined that choline plays an important role in memory.
Choline is an essential nutrient and the precursor molecule of acetylcholine, a neurotransmitter
found in cell membranes. Acetyl choline is required for proper muscle function and memory
consolidation (Ostrovskaya et. al, 2008).
Piracetam and aniracetam, two analogues of noopept, are currently used to treat
Alzheimer’s symptoms, but have no effect on many patients. Studies have found noopept to be
five-hundred times more effective than piracetam and aniracetam and researchers hope to begin
using it as a treatment for Alzheimer’s disease in the near future (Ostrovskaya et. al, 2006).
Considering recent studies and research, it can be concluded that administration of
noopept improves cognitive deficits resulting from neurodegenerative diseases. Studies involving
additional animal models may be necessary to evaluate the efficacy of noopept in a variety of
subjects. With additional studies, nootropic substances may finally provide a firm understanding
of Alzheimer’s disease, as well as a method of prevention or treatment (Ostrovskaya et. al,
2006).
Effects of Noopept on Alzheimer’s Symptoms 8
Bibliography
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Noopept Restores Spatial Memory and Increases Immunoreactivity to Amyloid in an
Alzheimer's Disease Model." Journal of Psychopharmacology 21.6 (2006): 611-19.
(2) Casaite, Vida et. al. "Expression and Purification of Active Recombinant Equine Lysozyme
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(3) Hauschild, A. et. al. "Melanoma Research." Melanoma Research 9.2 (1999). Prognostic
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