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CHEMICAL SIGNALLING
IN THE NERVOUS
SYSTEM
Chemical mediators:
-Neurotransmission
-Neuromodulator
-Neurotrophic factor
-Chemical mediator within the brain can
produce slow and long-lasting effect:
-they can act diffusely, at a considerable distance from
their site of release.
-they can produce diverse effect, e.g.:
-on transmitter synthesis
-on the expression of neurotransmitter receptors
-on neuronal morphology
In addition to affecting the ionic conductance of the post
synaptic cell membrane.
Neurotransmitter
-A substance released by one neuron and acting
rapidly, briefly and at short range on the membrane
of adjacent (postsynaptic) neuron, causing excitation
or inhibition.
Some types of neurotransmitter:
-acetylcholine
-monoamines (E, NE, dopamine, serotonin 5-HT, and
melatonin)
-amino acids, (glutamic acid, GABA, aspartic acid &
glycine)
-Purines, (Adenosine, ATP, GTP and their derivatives)
50
-Over
neuroactive peptides (vasopressin,
somatostatin, neurotensin, etc.) have been found,
among them hormones such as LH or insulin
-Single ions, such as synaptically-released zinc, are also
considered neurotransmitters by some.[
The major "workhorse"
neurotransmitters of the brain are
-Glutamic acid (=glutamate)
-GABA.
Glutamic acid is involved in cognitive
function:
-Nerve
impulses trigger release of glutamate from the pre-synaptic cell. In the opposing
post-synaptic cell, glutamate receptors, such as
the NMDA receptor, bind glutamate and are
activated.
- (NMDA (N-methyl D-aspartate) Calcium flux
through NMDARs is thought to play a critical
role in synaptic plasticity, a cellular
mechanism for learning and memory.
Synaptic Plasticity:
- is the ability of the connection, or synapse,
between two neurons to change in strength
including changes in the quantity of
neurotransmitter released into a synapse
and changes in how effectively cells respond
to those neurotransmitter
-Since
memories are postulated to be
represented by vastly interconnected
networks of synapses in the brain, synaptic
plasticity is one of the important
neurochemical foundations of learning and
memory
-In brain injury or disease, they can work in reverse
and excess glutamate can accumulate outside cells.
This process causes calcium ions to enter cells via
NMDA receptor channels, leading to neuronal
damage and eventual cell death, and is called
excitotoxicity.
-Excitotoxicity due to glutamate occurs as part of the
ischemic cascade and is associated with stroke and
diseases like amyotrophic lateral sclerosis(ALS) ,
lathyrism, autism, some forms of mental
retardation and Alzheimer's disease
GABA:
-GABA, or gamma-aminobutyric acid, is the most
abundant inhibitory neurotransmitter in the
brain.
- While GABA is an a.a, it is a neurotransmitter and
helps induce relaxation and sleep.
- It balances the brain by inhibiting over-excitation.
GABA contributes to motor control, vision, and many other cortical functions.
-Anxiety is also regulated by GABA. Some drugs that increase the level of GABA in the brain are
used to treat epilepsy.
Neuromodulator
-the action of which do not confirm to original
neurotransmitter concept.
-it covers not only the diffusely acting neuropeptide
mediators, but also mediators such as nitric oxide
and arachidonic acid metabolites which are not
stored and released like neurotransmitter, and
may come from non neuronal cells (glai) as well as
neuron.
Neuromodulator
-Neuromodulation relates to synaptic plasticity,
including short term physiological events such as
the regulation of presynaptic transmitter release
or post synaptic excitability .
Some types of neuromodulator
-Opioid peptides :
-Endorphins
-Enkephalins
-Dynorphins
-Substance P
Endorphins
-An endorphin produced by the pituitary gland that
is a potent pain suppressant.
- Beta-endorphin has the highest affinity for the μ1opioid receptor
μ-receptors are presynaptic, and inhibit
neurotransmitter release; through this
mechanism, they inhibit the release of the
inhibitory neurotransmitter GABA, and disinhibit
the dopamine pathways, causing more dopamine
to be released.
Substance P
-A short-chain polypeptide that functions as a
neurotransmitter especially in the transmission of
pain impulses from peripheral receptors to the
CNS.
- In the CNS, substance P has been associated in the
regulation of mood disorders, anxiety, stress,
reinforcement, neurogenesis, respiratory rhythm,
neurotoxicity, nausea / emesis and pain.
Neurotrophic factor
-Are released mainly by non-neuronl cells and act on
tyrosine kinas-linked receptors that regulate gene
expression and control neuronal growth and
phenotypic characteristic.
-Neurotrophic factors are small proteins that exert survivalpromoting and trophic actions on neuronal cells.
-During development, play a critical role in mediating the
ability of a target of a neuron to prevent the death of the
nerve cell.
-play a critical role in the "quality of life" of neurons.
- regulate growth of neurons, associated metabolic functions such as protein synthesis, and the ability of the
neuron to make the neurotransmitters that carry chemical
signals .
Glial cells (astrocytes):
-The main non-neuronal cells in the CNS and
outnumber neuron by 10 to1.
-Play an important signaling role.
-express a range of receptors and transporters
similar to those present in neuron , and also
release mediators (glutamate, lipid mediator and
growth factors)
-they respond to chemical signals from neurons,
from neighboring astrocyte and microglial cells.
-controlling the chemical environment in which the
neurons operate , surround neurons and hold
them in place, to supply nutrients and oxygen to
neurons, to insulate one neuron from another, and
to destroy pathogens and remove dead neurons.
Mediator types:
-Conventional small-molecule mediators
-Neuropeptides
-Lipid mediators
-Nitric oxide
-Neurotrophens, cytokines
-steroids
Conventional small-molecule
mediators:
-Examples
Glutamate, GABA, Ach, dopamine, 5-HT
-Main function:
fast synaptic neurotransmission neuromodulation.
-Targets:
ligand gated ion channels , G-protein-coupled
receptors
Neuropeptides:
-Ex.
Substance P, neuropeptide Y,
Corticotrophin releasing factor
-Main function:
neuromodulation.
-Targets:
G-protein-coupled receptors
Lipid mediatore
-Ex.
prostaglandins, endocannabinoid
-Main function:
Neuromodulation
-Targets:
G-protein-coupled receptors
Nitric oxide
-Main function:
Neuromodulation
-Targets:
Guanylate cyclase
Neurotrophens, cytokines
-Ex. nerve growth factor, brain derived
neurotrophic factor, interlukin-1
-Main function:
Neuronal growth, survival and functional plasticity
-Targets:
Kinase-linked receptor
steroids
-Ex.
Androgens, estrogens
-Main function:
Functional plasticity
-Targets;
Nuclear , membrane receptors
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