Neuroscience Module Undergraduate lecture

1. Dr Zahid Azeem
Department Biochemistry
AJK Medical College, Muzaffarabad
Class MBBS 2020,
Neurosciences Module

2. Definition
Neuropeptides represent large and diverse group
of molecules responsible for communication
among cells in the central nervous system (CNS).
their major effects are within the CNS, by taking part in
the regulation of thermoregulation, food and water
intake, circadian rhythms, and sexual and
reproductive behavior.
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3. Criteria
A molecule can be considered as a neuropeptide, when
it possesses distinct properties:
(1)Should be small-size protein molecule
(2)Should be produced and secreted by cells of the
nervous system, and
(3)Must play a specific role in the regulation of neuronal
cells
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4. Facts
At least in mammals, neuropeptides are encoded by
over 70 genes.
The size of the molecule is usually between 3 and 100
amino acids (AC), while more than 75% of known
neuropeptides have a molecule of less than 30 AC
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6. Synthesis
In contrast to the classic low molecular weight
neurotransmitters, neuropeptides are exclusively
produced inside the cell without local synthesis in
nerve endings.
In most instances, several different neuropeptides are
encoded by a single continuous messenger RNA
(mRNA), which is translated into 1 large protein
precursor (polyprotein).
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8. neuropeptides or their precursors are processed in
the endoplasmatic reticulum and then move to the
Golgi apparatus to be processed further.
They leave the Golgi apparatus within secretory
granules and are transferred to terminals by fast
axonal transport
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9. Synthesis
Neuropeptide synthesis takes place mostly in a
physiologically inactive form as the pre-pro-
molecules. The precursor, before being stored or
released from the cell, is typically degraded to short
chain of AC through endopeptidases in the Golgi
apparatus or directly in the secretory vesicles.
Nevertheless, some neuropeptide molecules undergo
further posttranslational modifications, necessary to
ensure their stability and full biological activity, such
as phosphorylation, acetylation, sulphonation, or
removal of their terminal part.
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10. Metabolic changes necessary to achieve a fully active
form of the neuropeptide are sometimes so intensive
that the result leads to an extreme shortening of the
peptide chain. Particularly, thyrotropin releasing
hormone (TRH) consists only of three amino acids,
compared to its much larger pre-pro-form.
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11. Secretion of Neuropeptides
Neuropeptides are secreted from large dense core
vesicles by regulated secretion.
They may be stored in vesicles together with other
low molecular weight neuropeptides or even with
other neurotransmitters.
Their secretion is not necessarily limited to the
synaptic cleft; however it usually occurs in the close
vicinity. There are also reported cases of secretion
from the cell body or from dendritic spines.
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13. Neuropeptides play a crucial role in cell-to-cell
communication by affecting
 gene expression,
synaptogenesis,
and modulation of membrane excitability.
Some neuropeptides even may act as
neurotransmitters.
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15. physiological effects of many neuropeptides, time of
their biological activity in the circulation is
significantly limited.
For instance, oxytocin has a half-life in blood of
approximately 120 seconds. Compared to the half-life
in the CNS extracellular space, which is about 20
minutes
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16. Receptor Binding
Diffusion through the extracellular space and binding
to membrane receptors are in a case of robust
neuropeptide much slower, however it is more solid
Most neuropeptides have their own specific receptor
coupled with G-protein.
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18. Although the size of neuropeptide molecules is
relatively large compared to classical
neurotransmitters, affinity to the specific receptors is
approximately 1000-fold higher than that of the
neurotransmitter, thus being capable of biological
response at lower concentrations
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19. Classification of Neuropeptide
Up to date, the different databases (NeuroPep,
NeuroPedia, http://www.neuropeptides.nl/ cover over
5900 neuropeptides divided into large groups. While
the number of neuropeptides in vertebrates reaches
nearly 2500.
The division into families may be based on similarities
in the gene structure
e.g., calcitonin gene family,
F- and Y-amide gene family.
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20. Molecule structure
e.g., oxytocin/vasopressin family,
insulin/insulin-like growth factor (IGF) family),
Function
e.g., opioid neuropeptide family,
adipose neuropeptide family,
Localization of neurons producing each neuropeptide
E.g. 1- hypothalamic neuropeptide family,
2- hypophyseal neuropeptide family.
Many novel neuropeptides remain unclassified. 20

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Effect of Neuropeptide on neurogenesis

22. Different Neuropeptides
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23. Substance P
1- Substance P (SP), an 11-amino acid peptide, is a
member of a family of structurally related peptides
called tachykinins, which are characterized by a
conserved carboxyl terminal sequence of
Phe-X-Gly-Leu-Met-NH2
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24. Substance P is present in many areas of the CNS and
PNS. In the periphery, SP is located especially in areas
of immunologic importance, such as the skin,
gastrointestinal tract, and respiratory tract.
Substance P is synthesized in the dorsal root ganglia,
from which it migrates centrally to the dorsal horn of
the spinal cord and peripherally to nerve terminals of
sensory neurons.
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25. Calcitonin Gene-Related
Peptide
Calcitonin gene-related peptide (CGRP), a 37-amino
acid peptide, is known to exist in 2 forms, alpha and
beta. In humans, they differ from each other by 3
amino acid residues.
alpha-Calcitonin gene-related peptide is encoded by the
calcitonin gene.
The expression of either CGRP in the CNS or calcitonin
in the thyroid is tissue related. In contrast, beta-CGRP
is the sole biologically active product of a separate
gene.
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26. Stimulation of CGRP receptors in various cells and
tissue has been shown to increase intracellular cyclic
adenosine monophosphate (c-AMP) concentration
and to activate adenylate cyclase.
Calcitonin gene-related peptide is present in small
sensory neurons partially colocalized with SP.
Peripheral secretion of CGRP causes prolonged
increases in blood flow.
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27. Neuropeptide Y
Neuropeptide Y is a polypeptide containing 36 amino
acid residues that is closely related to pancreatic
polypeptide. It is present in many parts of the brain
and the autonomic nervous system.
In the autonomic nervous system, although not in the
brain, much of it is located in noradrenergic neurons,
from which it is released by high-frequency
stimulation.
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28. Neuropeptide Y
It augments the vasoconstrictor effects of
norepinephrine. Circulating neuropeptide Y from
sympathetic nerves.
increases with severe exercise in humans. Evidence is
accumulating that in the hypothalamus,
It mediates increased appetite and increases in food
intake.
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30. NEUROPEPTIDES AND BEHAVIOUR
Many different peptides evoke specific effects on
behaviour. For example,
1- oxytocin is involved in social behaviours, including
bonding and maternal behaviour,
2- and vasopressin acts in the brain to affect social
recognition and aggression.
Other nerve cells release other peptides and they have
effects on other emotions and behaviours.
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31. Vasopressin and oxytocin have been linked to human
neurological disorders such as
1- social anxiety disorder
2- depression,
3- schizophrenia and
4- autism spectrum disorder.
In addition, disorders of appetite regulation, libido, and
mood are among many potential targets of peptide-
based therapies.
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32. In the future, ‘sniffing’ neuropeptide analogues
(intranasal administration) may open a gateway to the
brain, and diffusion of the peptides to its receptor
sites may be an alternative way for treatment of some
of these disorders.
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33. Thanks
Have a nice Day ahead
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