NEURO-BIOCHEMISTRY

 OUTLINE
 Introduction
 Definition of concepts
 Action potential and transmission of impulse
 Types of synapse
 Mechanism of synaptic neurotransmission
 Neuroplasticity
Introduction
 Neurobiochemistry as an aspect of biochemistry is concerned

with the study of neurochemicals, neurons,

psychopharmaceuticals, neuropeptides and their interactions/
influences on the entire processes occurring in the nervous
system.

 It is also the scientific study of the biochemistry of nerve cells

and how molecules, such as proteins and lipids, affect the
nervous system

 It encompasses the brain, nervous system and transmission of

impulses.

 An in-depth knowledge on neurobiochemistry will aid the

understanding into the molecular basis of diseases related with
the nervous system, brain and neurons.
 Definition of Concepts
 Neurons: This is the basic cell unit in the nervous system
and the brain and is responsible for signal transmission
(sending and receiving of signal).

 It is made up of a cell body (soma) from which long axons

and short dendrites protrude and a myelin sheet that
protects the axon.

 Soma contains the nucleus and cytoplasm

 Axon is responsible for signal transmission
 Dendrite is responsible for receiving information
 Myelin protects the axon
Structure of the neuron
 Synapse: This is the axon-dendrite connection.
 It is a point where two neurons meet and allows for

exchange of impulses.
 A small gap called synaptic cleft is formed between two

neurons hence creating the need for a transmitter to aid

the transmission of chemical or electrical impulses.
 Axon of one neuron forms the pre-synaptic cleft while

the dendrite of the other forms the post-synaptic cleft.

 Synapses can be excitatory: they depolarize membrane

potentials of post-synaptic neurons, increasing the action

potential or
 Inhibitory: they hyperpolarize the membrane potential

of post-synaptic neurons, decreasing the action potential.


 Nervous System
 This is a collection of nerves, fibres, nerves cells

responsible for the transmission of impulses to various parts

of the body and supporting cells called neuroglia.
 The neuroglia is made up of glial cells (astrocytes and

oligodendrocytes), microglial cells, ependymal cells and

Schwann cells
 These neuroglia support and sustain the neurons by holding

them in place, supplying nutrients and oxygen to the

neuron, insulate the neurons to ensure that their signals are
transmitted and clean up debris that enters the nervous
system
 The functions of these cells are shown in the table below
Cells Location Function
Astrocytes CNS Guides neuronal migration to
their final position and keeps
neuron in place. Other functions
include: phagocytosis, supply of
lactate control of brain
extracellular ionic environment
and regulating contents of ECF
Oligodendrocytes CNS Provides myelin sheet, serves as
insulator for neurons, forms a
matrix with astrocytes for
neurons. Can myelinate multiple
axons
Schwann cells PNS Forms myelin around the axons
but myelinate only one axon,
remove debris in PNS, helps
peripheral axons regenerate
when damaged
Microglial cells Nervous system Smallest cells, serve
immunological function like
macrophage, destroy microbes
and phagocytose cellular debris
Ependymal cells CNS and Spinal Cord Secrete CSF into the ventricular
system, allows proper circulation
of CSF in the CNS. CSF acts as a
shock absorber protecting the
CNS from mechanical trauma
and removes metabolic wastes.
 The nervous system is classified broadly into two:
Central and Peripheral nervous system as shown
Action Potential and the Transmission of Impulse
 Signal transmission from the central nervous system to

any target cell is due to the transmission of action

potential.
 Action potential is defined as a short electrical impulse

that aids signal transmission along the axon of a neuron.

 For signal to be transmitted, a potential difference of

the electrical impulse must be established inside and

outside the neuron and it is known as the membrane
potential.
 When the neuron is resting and not transmitting any

impulse, a resting potential is established.

 The maximum membrane potential that must be

achieved before signal can be transmitted is known as

the threshold potential.
 Prior to the transmission of impulse, the neuron with a
resting potential undergoes a series of processes as
described in the Figure below
Types of synapses:
 A nerve impulse is an electrical signal that moves along the

neural pathway until it reaches the end.

 The electrical signal is converted to a chemical signal at

the synapse, while it passes through the pathway and

converted back to electrical signal.
 A synapse is a junction through which a neuron relays

information to another neuron; it characterized by three (3)

main components: Axon terminal, synaptic cleft and the
dendrite.
 Synapse can be chemical or Electrical. The main difference

is that in a chemical synapse, the nerve impulse passes

chemically by means of neurotransmitters whereas an
electrical synapse is connected through channel proteins.
Electrical synapse
 An electrical synapse transmit nerve impulses by means of

ions.
 Electrical synapses are fewer in number than chemical

synapses.
 Signalling is instantaneous (very fast) and this is important for

synapses involved in key reflexes, e.g retina, olfactory bulb,

cerebral cortex, lateral vestibular nucleus, and hippocampus.
 Most electrical synapses are bidirectional.

 Mode of neurotransmission in the electrical signal involves the

gap junction; a channel of protein connecting the very close

postsynaptic and presynaptic membranes.
 Gap junctions allow electrical signals (current) to pass

directly(diffuse) from one cell to the next, so also the ions that
carry these current, other molecules, such as ATP.
 Synaptic cleft in electric synapse is smaller in size (0.2 nm)
Chemical synapse
 A chemical synapse aids the transmission of nerve impulses in

one direction using neurotransmitters.

 It involves the presynaptic (transmitting neuron), synaptic

cleft and postsynaptic (Receiving neuron) cells.

 Signalling is slow compared to electrical synapse due to the

dependence on the release of neurotransmitter molecules from

synaptic vesicles before passing their signal.
 Hence, there is an approximately one millisecond delay

between when the action potential reaches the presynaptic

terminal and when the neurotransmitter leads to opening of
postsynaptic ion channels.
 They are found in nervous systems, principally at neuron

junctions of higher vertebrates.

 Chemical synapses are unidirectional.

 They have larger synaptic cleft (10-20 nm).

Schematic representation of chemical synapse
Similarities between Chemical and Electrical Synapse
 Chemical and electrical synapses possess synaptic

clefts.

 Chemical and electrical synapses transmit nerve

impulses between neurons or between neurons and
effector organs.
Mechanism of synaptic neurotransmission
 Biosynthesis of neurotransmitters: Neurotransmitters

are synthesized from various precursors and stored in

the synaptic vesicles in the axonal terminals.
 Arrival of action potential at axonal terminals: A

graded potential above the threshold action potential,

or nerve impulse, arrives at the axon terminal, which
depolarizes the membrane and opens voltage-gated Na +
channels. Na+ ions influx into the cell, further
depolarizing the presynaptic membrane, causing the
voltage-gated Ca2+ channels to open, such that Ca2+,
which is present at a much higher concentration outside
the neuron than inside, flows rapidly into the cell.
 Release of neurotransmitter: Calcium ions entering the
cell initiate a signaling cascade (Ca 2+ →Calmodulin→
Protein kinase→ phosphorylation of membrane proteins),
that activate small membrane-bound vesicles, called
synaptic vesicles, containing neurotransmitter molecules.
 At the binding of the calcium ions to synaptic vesicle
membrane protein (Synaptotagmin), synaptic vesicles
fuse with the presynaptic membrane, the synaptic vesicle
proteins begin to move apart, creating a fusion pore, the
pore allows the release of neurotransmitter into the
synapse, then the neurotransmitter will be released into the
synaptic cleft by exocytosis.

 This added membrane is later retrieved by endocytosis and

re-used for the formation of fresh neurotransmitter-filled
vesicles.
 Binding to postsynaptic receptors: The neurotransmitter
diffuses across the synaptic cleft and binds to receptor
proteins on the postsynaptic membrane.

 In the case of ligand-gated channels, the neurotransmitter

causes the postsynaptic membrane to open, resulting in a
localized depolarization (excitatory postsynaptic potential
(EPSP)) or hyperpolarization (Inhibitory postsynaptic
potential (IPSP)) of the postsynaptic neuron.

 In some instances, the receptor though not an ion channel

itself, activates ion channels using a signaling pathway.
 Inactivation of neurotransmitter: After neurotransmission is
concluded, the neurotransmitter must be removed from the
synaptic cleft so that the postsynaptic membrane can return
(reset) and be ready to receive another signal.

 The neurotransmitter can be removed either by diffusion from

the synaptic cleft or enzymatic degradation or recycle (which
involve the active reuptake of neurotransmitter for reuse).

 Note: When postsynaptic receptors are activated, it leads to

the opening or closing of ion channels in the cell membrane,
and this may be depolarizing (increasing the positivity inside
of the cell) or hyperpolarizing (making the inside of the cell
more negative), based on the ions concerned.
 Some neurotransmitters also have a neuromodulatory action.
 These can act on so many neurons at once and aids larger
scale regulation of groups of neurons. This process is much
slower than excitatory and inhibitory transmission

Diagram showing the basic model of a chemical synapse in

neurotransmission
Neuroplasticity
 This term describes the changes in neurons and
neuronal networks in the brain that occur in response to
electrical and chemical signals.
 The brain tissue is not a static structure; rather it

changes in response to the stimulus it receives from the

environment.
 Neuroplasticity is the basis for understanding the brains

ability to receive and store information as memories

and to retrieve it in response to relevant environmental
cues
 The mechanism of neuroplasticity involves potentiation
where the flow of information increases as more signals
pass through and depression, where the flow of information
through a neural pathway decreases in response to
decreased signals through it.

 These processes are realized at two levels of the neural

network: synaptic and structural.

 At the synaptic level, potentiation involves the synthesis

and insertion of neuroreceptors within the cell membrane
at the synapse while depression results in a decrease in the
number of neuroreceptors.
 At the structural level, changes in the structure of the
neuron by an increased in the number of dendrites are
common in potentiation, while a reduction in the
neuron branching is a common feature of depression.
 The changes in potentiation serve to reinforce the

strength and frequency of signals passing through

neural networks, a necessary activity for learning and
memory storage.

 Developmental neuroplasticity is the term used to

describe the long-term changes that occur in the
brain’s neuron structure, synaptic networks as it
develops from childhood to adulthood.