ROLE OF NEUROTRANSVITTERS IN THE MEDIATION OF SPEECH AND

LANGUAGE

DEFINITION:

Neurotransmitters are endogenous chemicals which relay, amplify, and modulate signals
between a neuron and another cell

a) Neurotransmitters are small molecules that are liberated by the pre synaptic neuron
into the synapse cleft that cause change in post membrane potential
b) These chemicals are prod west within he cell body of a neuron. They travel along the
neuron's axon and take up residence in the vesicles, which are essentially small pods
c) Filled with neurotransmitter White the neuron receives the correct impulse, a vesicle
will burst open to release the corresponding neurotransmitter, and the chemical will
travel across the synapse receptors located on the dendrites of a neighbouring neuron
or neurons.

Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on
the presynaptic side of a synapse.

They are released into the synaptic cleft, where they bind to receptors in the membrane on the
postsynaptic side of the synapse.

Release of neurotransmitter usually follows arrival of an action potential at the synapse, but
may follow graded electrical potentials.

Criteria to define neurotransmitters.

1. Synthesis: the molecule should be synthesized in presynaptic neurons.

1. Localization: Should be present in the presynaptic terminal
2. Release: the substance must be released in response to pre-synaptic depolarization
and the release must be Ca2+ dependent.
3. Specific receptors for the substance must be present on post-synaptic cell.
4. Response mimicry: when experimentally applied, the molecule should produce a
response that is similar to the endogenous release of neurotransmitter.
5. Inactivation: a specific mechanism should exist to remove the molecule from the
synaptic cleft or to degrade it.
TYPES OF NEUROTRANSMITTER

Major Neurotransmitter

(Fall into one of the three chemical categories)

Small Molecule NT Large Molecule NT

Biogenic amines Amino Acids Neuro-peptides

Acetylcholine GABA Cholesystokinin

Dopamine Glutamate Enkephalins

Epinephrine Glycine Somatostatin

Nor-epinephrine Neuropeptide

Serotonin

Histamine

Acetylcholine

a) Acetylcholine (Ach) was the first NT to be discovered. It is found both in the central
nervous system and the peripheral nervous system.
b) Acetylcholine is an excitatory neurotransmitter(but not always).
c) Ach synthesis is made in one step from Acetyl coenzyme(acetyl CoA) and choline
d) Acetyl Cod is formed in the brain during the process of metabolism of glucose with the
help of oxygen to produce ATP.
e) Choline is not manufactured by the brain so it is obtained from foods that are rich in
choline like egg yolk and many other vegetables.
f) The enzymes that facilitate the synthesis of Ach are Acetyl Co and choline
acetyltransferase which are always present in the body.

Synthesis and activation of Ach

a) Ach is formed at the axon terminals or synthesized in the cell body of the neuron and
is transported down the axon to the terminals. It is then synthesized from choline by
Acetyl CoA in a reaction which is catalysed by Choline Acetyltransferase.
 b) The voltage gated Calcium channel is opened when the action potential reach the
terminal bottom of the pre-synaptic neuron and the Ach is released into the synaptic
cleft by the vesicles when the calcium ions rush onto them.
c) The diffused Ach molecules binds to their recpetors which leads to an influx of
potassium ions which results I depolarizing of the post synaptic neuron.
d) The initiation of a new action potential takes place.
e) Once the Ach binds to it receptors Choline Acetyltransferase enzyme break it down to
acetate and choline which are reused.

Function of the Ach as a neurotransmitter

A. In the peripheral nervous system

a) In the peripheral nervous system, acetylcholine activates muscles, and is a major

neurotransmitter in the autonomic nervous system. When acetylcholine binds to acetylcholine
receptors on skeletal muscle fibers, it opens ligand-gated sodium channels in the cell
membrane. Sodium ions then enter the muscle cell, initiating a sequence of steps that finally
produce muscle contraction. Although acetylcholine induces contraction of skeletal muscle, it
acts via a different type of receptor (muscarinic) to inhibit contraction of cardiac muscle
fibers.

b) In the autonomic nervous system, acetylcholine is released in the following sites:

c) all pre- and post-ganglionic parasympathetic neurons

d) all preganglionic sympathetic neurons

preganglionic sympathetic fibers to suprarenal medulla, the modified sympathetic

ganglion; on stimulation by acetylcholine, the suprarenal medulla releases epinephrine and
norepinephrine.

e) Some postganglionic sympathetic fibers.

Pseudomotor neurons to sweat glands

B. In the Central Nervous System

a) in the CNS, Ach has a variety of effects as a neuromodulator upon plasticity, arousal and
reward. Ach has a important role in the enhcancement of sensory perceptions when we wake
up and in sustaining attention.

b) Damage to the acetylcholine-producing system in the brain has been shown to be plausibly
associated with the memory deficits associated with Alzheimer’s disease. Ach has also been
shown to be the most important inducer of REM sleep
c) there are three Ach pathways in the CNS

i. Pons to thalamus and cortex.

ii. Magnoccllular forebrain nucleus to cortex.

ii. Spetohippocampal

Plasticity

Ach is involved with synaptic plasticity, specifically in learning and short-term memory.

In general the functions of ACH are as follows

a) ACH activates muscles, and is a major neurotransmitter in the autonomin nervous

system.
b) Ach is excitatory in function by stimulating muscle contraction while
c) It inhibits contraction in cardiac muscle fibers showing its inhibitory functions.
d) In the CNS, ach has a variety og effects upon plasticity, arousal and reward.
e) Helps in enhancement of sensory perseptions when we wake up and in sustaining
attention.
f) It controls REM stage of sleep.
g) Involved in wakefulness, anger, aggression, etc.
h) Acetylcholine is critical for an adequately functional memory.

Ach & Dementia in Alzheimer’s Disease

a) The amount of Ach in patients with Alzheimer’s disease is less because:

i. Nerve cells where the Ach is produced die

ii. Cholinergic neurons in the forebrain region and hippocampus containing the Ach
receptors die.

b) The loss neurons is progressive.

Features of Alzheimer’s Disease

a) Impairment in memory.
b) Depression
c) Violence
d) Disorientation
e) Circumlocution
f) Poor reasoning skills
g) Hallucinations and delusions
h) Intellectual disorientation
i) Impairment of semantics and pragmatic functions
j) Preserved synaptic and phonological skills.
Treatment through drugs

Cholinesterase inhibitors is given to inhibit AChE, the enzyme that degrades acetylcholine in
the synapses.

Ach in Adults in Down Syndrome

Some studies carried out on adults with Down Syndrome has shown that there is significant
reduction in ChAT- the enzyme involved in Ach synthesis.

Dopamine

a) Dopamine is a CATECHOLAMINE as it contains Catechol ring.

b) Dopamine is inhibitory in nature, i.e., when it finds its way to its receptor sites, it blocks de
tendency of that neuron to fire.

c) It is synthesized in the cytoplasm

d) It is secreted by neurons that originate in the basal ganglia and cerebral cortex.

e) Major Dopamine containing area in brain is the corpus striatum whose input is majorly
from Substantia Niagara and Ventral tegmental area.

c) Dopamine activity is more in the left hemisphere than in the right and more in the dorsal
area (in the frontal lobe) compared to lateral and medial areas.

Synthesis and activation of dopamine

a) The synthesis of dopamine is simple. Tyrosine is an amino acid that is present in the
protein rich food that we eat.

b) Tyrosine is converted to L-DOPA with the help of the enzyme Hydroxylase and this L-
DOPA; converted into Dopamine by the action of Dopa Decarboxylase.

c) The Tyrosine is transported down the axon to the terminals where the synthesis of
Dopamine takes place and it is stored in the vesicles.

d) As the action potential arrive at the terminals, the calcium ions flow into the terminals and
dopamine is released from the vesicles

The diffused dopamine in the symaptic cleft then attach to the respective receptors and cause
changes in the post synaptic membrane. The receptors release the dopamine and some of it is
diffused back and taken up by the pre-synaptic terminal
Functions of Dopamine as neurotransmitter

Movement - Dopamine is a crucial part of the basal ganglia motor loop. This means that it is
absolutely critical to the way our brain controls our movements. Shortage of Dopamine
causes Parkinson's disease, in which a person cannot execute smooth, controlled movements.

Pleasure and Motivation- Dopamine is connected with the pleasure system of the brain.
This means that is provides feelings of enjoyment and reinforcement which motivates us to
do or to continue doing certain activities. Drugs seem to be directly or indirectly related to the
increase of dopamine in the brain, and therefore are addictive in nature.

However, after a while, the brain grows accustomed to the increased amount of Dopamine
brought about by the drugs. Therefore, if the intake of drugs is suddenly stopped, it could
have an opposite reaction such as depression

Also, when aversive or unpleasant stimuli are encountered, dopamine is released. This
suggests that it is not associated only with pleasure. Dopamine is also released when a
pleasurable activity is expected to happen.

This tells us that the activity does not even have to actually take place for dopamine to be
released.

Therefore, it could be more involved in 'desire' rather than 'pleasure

Cognition and Frontal Cortex function- Dopamine controls the flow of information to
other parts of the brain. This occurs in the frontal lobes. In the frontal lobe, it is believed to
control flow of information from other areas of the brain which control attention, memory
and problem-solving. Disorders in this part of the brain can cause a decline in memory,
problem solving and attention. Neurocognitive functions as a whole, suffer a downfall.

a) It plays an important role in habit forming substances.

b) It is important for performing balanced, controlled movements and posture,
coordination of body movments.

Dopamine in Parkinson's disease

i. Neurochemically, parkinsonism involves reduced levels of dopamine. Dopamine

neurons in the nigrostriatal pathway (one of the pathways through which
dopamine acts) die.
ii. Dopamine and ACh neurotransmitters should normally be in balance. But in
parkinsonism, as the level of dopamine reduces, there is an excess of Ach which
can be the reason for the molo symptoms like rigidity, tremor, akinesia,
impairment in co-ordination, balance.
iii. Other symptoms are depression, errors of prosody & articulation.
iv. Patients with parkinsonism have masked like face.
Treatment through drugs

1. Drugs to increase dopamine (e.g Levadopa) can be given or

2. Drugs to diminish ACh (Anticholinergics like artane, cogentin) can be given to the patient.

Dopamine in normal ageing & Parkinsonism:

Dopamine levels fall in normal ageing

If it falls to 1/5th of its normal (original) value, then Parkinsonism is said to occur.

Dopamine in Schizophrenia

a) Excessive dopamine activity has been reported in the meso-limbic pathway of dopamine
neurotransmitter which causes Schizophrenia.

b) Abnormally low levels of glutamate receptors is also found to be one of the cause of
Schizophrenia.

c) Alterations in presynaptic dopamine function constitute a part of the disrupted neural

circuits that predispose people to schizophrenia. (Hieta la 1995)

d) The dopamine receptors involved in these processes can be separated into the D1 and D2
families.The D1 family contains the receptors D1 and DS. The D1 receptors in the brain are
linked to episodic memory, emotion, and cognition. These functions are disturbed in
schizophrenic patients. In addition, DI binding of dopamine was found to be lower in
schizophrenic patients as compared to healthy subjects of the same age. The binding was
lower as a result of fewer D1 receptors. Certain antipsychotic drugs stimulate D1 regulated
pathways, which increases the DI to D2 activity balance in the brain. This balance can also be
regained by the release of dopamine

e) The D2 family contains the receptors D2, D3, and D4. D2 is the second most abundant
dopamine receptor in the brain. D2 receptor blockade is the main target for antipsychotic
drugs, because there is a higher density of D2 in schizophrenic brains. (Sedvall & Farde
1995)
Nor- epinephrine/nor adrenaline

a) Nor-epinephrine (along with acetylcholine) is one of the two NT in the peripheral nervous
system.

b) It is secreted by many neurons which are located in the brain stem and hypothalamus.

c) The release of norepinephrine is typically precipitated by stress, either physical or

psychological

Synthesis and activation

a) Nor-epinephrine is synthesized from Dopamine with the help of enzyme Dopamine-Beta-

hydroxylase with oxygen, copper and vitamin C as co- factors.

b) As the action potentials arrive at the terminals, calcium ions flow into the terminals
releasing the Nor-epinephrine from the vesicles into the synaptic space.

c) The diffused Nor-epinephrine attach to the respective receptors and cause change in the
post synaptic membrane.

d) Some of the diffused nor-epinephrine is taken up by the pre synaptic terminal.

Functions

a) It is excitatory in nature.
b) Norepinephrine also activates the central and sympathetic nervous system in what is
referred to as the "fight-or-flight" state. It contributes to increases in attention and
reaction time.
c) Norepinephrine has several effect on the vascular system, including dilation of blood
reset, increased heart rate and increased blood pressure.
d) It is also important in maintaining attention and forming memories.
e) important for attentiveness, emotions, sleeping, dreaming, and learning
f) It helps in emergency response.
g) It is responsible for selective and sustained attention.
h) Active projection of Nor-epinephrine in the forebrain is a key feature of awareness-
arousal as distinguished from sleep.
i) Its projection to the basal nucleus of the forebrain is low in sleep and virtually absent
in REM (Rapid Eye Movement) sleep.
j) Norepinephrine will also cause an increase of glucose production in the liver, which
can serve as a fast energy source in a stressful situation.

Norepinephrine also triggers the pituitary gland to release a hormone called ACTH,
adrenocorticotropic hormone. ACTH effects the adrenal cortex, causing it to release cortisol,
which contributes to making the adrenal medulla cease production of norepinephrine.
ADHD and NOREPINEPHRINE

a) ADHD is a disruptive behavior disorder characterized by the presence of a set of

chronic and impairing behavior patterns that display abnormal levels of attention,
hyperactivity or their contribution (DSM-IV).
b) According to the study "Attention Deficit/Hyperactivity Disorder as a noradrenergic
Disorder"- Bio Psychiatry Journal. 1999 reveals that.
c) The Norepinephrine system has been intimately associated with the modulation of
higher cortical functions including attention, alertness, vigilance and executive
functions
d) Norepinephrine activation is known to profoundly affect the performance of attention,
especially the maintenance of arousal, a cognitive function known to be deficient in
ADHD.

Serotonin

a) Serotonin is a monoamine neurotransmitter.

b) It is inhibitory in nature.
c) 80-90% is synthesized in the gastrointestinal tract, where it is used to regulate
intestinal movements.
d) Remainder is synthesized in serotonergic neurons in the central nervous system
(CNS)
e) The cell bodies of serotonin containing neurons in the brain are situated in a narrow
band of nuclei that run along the brain stem from the medulla to the mid brain which
are called the Raphe nuclei.

Synthesis and activation of serotonin

a) It is synthesized from Tryptophan

b) Tryptophan is a naturally occurring amino acid.
c) Tryptophan is converted into an intermediate product called 5-hydroxytryptamine(S-
HTP) with the help of the enzyme tryptophan hydroxylase. 5-HTP is later converted
into Serotonin.
d) Tryptophan is transported down the axon to the terminal where it is converted to
serotonin.
e) Once the action potential arrive at the serotonin terminal, serotonin molecules are
released into the synaptic cleft and act on the respective receptors on the surface of
the post synaptic neuron.
f) The serotonin is then released from the receptors and taken back up the terminals.

Functions of serotonin as neurotransmitter

 1. Memory
2. Learning
3. Emotions
4. Wakefulness
5. Sleep
6. Temperature regulation
7. Mood
8. Controlling anxiety
9. It plays a role in sensory perception
10. Serotonin is implicated in a variety of the cardiovascular, renal, immune and
gastrointestinal systems
11. Serotonin is implicated in a variety of physiological tasks, including learning and
memory in the CNS and emesis and peristaltic reflex in the ENS. Serotoninc-active
drugs are used as antidepressants and anti-anxiety drugs.

Serotonin has

a) An excitatory effect on motor pathways and

b) An inhibitory effect on sensory pathways.

c) The discharge in serotonergic neurons in the dorsal raphe nucleus cause Migraine.

Serotonin and depression

a) Serotonin is a psychiatric disorder characterized by sad mood, loss of pleasure, guilt,

disturbed sleep and appetite. There is sufficient evidence that suggest that depression may
have a neurochemical etiology based in levels of serotonin. This is referred to as the
indoleamine hypothesis of depression.

b) Low serotonin levels are believed to be the cause of many cases of mild to severe
depression which can lead to symptoms such as anxiety, apathy, fear, feelings of
worthlessness, insomnia and fatigue.

The newest medications used to suppress depression are collectively known as selective
serotonin inhibitors (SSRIs). SSRIs work by altering the function of neurons that release
serotonin by blocking the reuptake of serotonin back into the cell. Therefore the level of
serotonin activity is increased in any part of the nervous system that uses this
neurotransmitter as a chemical signal between cells.

c) Depression has been linked to a lack of stimulation of the recipient neuron at a synapse. To
stimulate the recipient cell, SSRIs inhibit the reuptake of serotonin. As a result, the serotonin
stays in the synaptic gap longer than it normally would, and has the chance to be recognized
again (and again) by the receptors of the recipient cell, which can finally be stimulated that
way
Serotonin syndrome

a) Serotonin syndrome is a condition caused by an excess of serotonin in the brain. Serotonin

syndrome may result from therapeutic drug use when a patient is more sensitive to the SSRI,
but it may also result from intentional self-poisoning or self-medicating.

b) The tricyclic antidepressants, lithium, MAOIs, SSRIs, ECT (electric shock treatment),
tryptophan, and the serotonin agonists (fenfluramine) all enhance serotonin
neurotransmission and can contribute to this syndrome. The effects of serotonin syndrome
may progress from headaches, dizziness and vomiting, to coma and death. Serotonin
syndrome is a clinical triad of cognitive-behavioral changes, autonomic dysfunction and
neuromuscular dysfunction.

c) Serotonin syndrome is characterized by cognitive and behavioural changes, autonomic

dysfunction and neuromuscular abnormalities. The syndrome often occurs within hours or
days of the addition of a new medication or the increment in dosage of the serotomimetic
agent which affects serotonin metabolism.

Serotonin in Autism/PDD

a) Autism is a brain-based, non-progressive Pervasive Developmental Disorder (PDD) that

exhibits symptoms in three areas of human development: socialization, communication and
behavior. In individuals with autism, ' reciprocal social interaction and communication' are
significantly impaired.

b) Sensory integration and emotional behavior may abo be affected. Autism individuals may
be withdrawn and react unusually to other people. Repeated movement hand flapping, or
display an unusual attachment to selected objects. They also may be aggressive toward others
or themselves and often have a marked resistance to changes in routine.

c) The causes of autism are widely debated, but a substantial body of research exists that
shows differences between autistic and non-autistic individuals in the structure of the brain,
'electrical wiring' and the level of certain neurotransmitters in blood and spinal fluid. One
such neurotransmitter is serotonin which is instrumental in the control of sleep, mood, some
types of sensory perception, body-temperature regulation and appetite.

d) It also affects the rate at which hormones are released and has something to do with tissue
inflammation. Individuals with Autism are known to have increased levels of serotonin in
their blood. They produce, absorb or metabolize serotonin differently than those who are not
autistic.
Gama amino butyric acid (GABA)

Synthesis and activation of GABA

a) GABA is formed within GABAergic axon terminals and released into the synapse,
where it acts at one of two types of receptor: GABAA, which controls chloride entry
into the cell, and GABAB, which increases potassium conductance, decreases calcium
entry, and inhibits the presynaptic release of other transmitters.
b) Y-Aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the central
nervous system.
c) It is highly concentrated in sustantia miagra and globus pallidus nuclei of the basal
ganglia, followed by hypothalamus and hippocampus.
d) GABA is a simple amino acid that is synthesized from glutamate in one step.
e) Glutamate is converted into GABA with the help of Decarboxylase.
f) When the action potentials reach the terminals, the calcium chennels open the calcium
ions rush in releasing GABA from the vesicles. The released GABA combines with
the GABA receptors.
g) There are no enzymes that break down or inactivate GABA instead after it is released
from the receptors much of it is diffused back across the synaptic cleft and is taken up
the pre synaptic terminal and stored in the vesicle. The synthesized and stored GABA
is re used when required again.

Functions of GABA

a) It is inhibitory in nature.

b) Contributes in motor control, vision and many other cortical functions.

c) It acts like a break to the excitatory neurotransmitters that lead to anxiety.

d) Lack of GABA in some parts of the brain results in epilepsy.

Epilepsy and seizure

a) Seizures is defined as an abnormal, disorderly discharging of brain's nerve cells resulting

in temporary disturbance of motor, sensory or mental functions.

b) The term seizure refers to a transient alteration of behavior due to abnormal synchronized
and repetitive bursts of firing of neurons in the central nervous system.
c) Epilepsy is a brain disorder that causes recurrent seizures.

d) Epilepsy is abnormal electrical activity on one side of the brain which spreads to other side
of the brain via the corpus callosum connecting the two hemispheres causing severe seizures.
(Sperry 1981).

i. Epilepsy is caused by an imbalance between excitatory and inhibitory

neurotransmitters especially Glutamate and GABA.

ii. If the inhibitory NT in the brain are not active enough or if the excitatory ones are too
active, then it is more likely to have seizures.

e) When there is too little GABA, it reduces transmission and the other neurons begin to
transmit uncontrolled Epileptic impulses

f) Drugs foe epilepsy are as follows:

i. VIGABATRIN: It suppresses epilepsy by enhancing the activity of GABA

ii. Epilim for seizures

iii. Zarotin for Epilepsy

g) Most epileptic drugs have side effects.

Landau-Kleffner syndrome

a) Landau-Kleffner syndrome (LKS), also called infantile acquired aphasia, acquired

epileptic aphasia or aphasia with convulsive disorder, is a rare, childhood neurological
syndrome.

b) It is named for William Landau and Frank Kleffner, who characterized it in 1957

c) Acquired aphasia is the more prominent feature, since seizures are present in only 70% to
80% of the patients (Beaumanoir 1985; 1992; Paquier et al 1992). Age of onset ranges from 3
to 8 years, and boys are more frequently affected than girls (Beaumanoir 1985).

d) The onset of aphasia is often insidious and progressive with spontaneous improvements
and aggravations in its course. The most common feature is verbal auditory agnosia, which is
the reason that in many cases the first diagnosis is hearing loss (Rapin et al 1977). Agnosia
may extend to familiar noises.

e) In some cases onset may be abrupt, and different types of aphasia may occur (Soprano et al
1994). Variable time may elapse between the loss of the ability to understand language and
the expressive aphasia.
f) In general, it is stated that patients previously had been normal in both psychomotor and
language development. However, detailed history of language characteristics show that 9 of
12 patients have had previous features of developmental dysphasia (Soprano et al 1994).
Very rarely, stuttering may be the presenting feature (Tutuncuoglu at al 2002), although it is
quite difficult to differentiate pure stuttering from the repetitive nature of the impaired speech
in early stages of acquired aphasia.

1) Seizures are present in 70% to 80% of patients and may appear before or after onset of
aphasia (Donna et al 1977). The most common types of seizures are: eyelid myoclonia, eye
blinking, atypical absences, head drops and atonic fits in upper limbs, automatisms, and
occasionally, partial motor seizures with secondary generalization.

Glutamate (glutamic acid)

a) Most common NT in the Brain.

b) Nearly all CNS excitatory neurons are glutaminergic and around half of the brain synapse
release it.

c) It plays an important role in synaptic plasticity. It is involved in cognitive functions like

learning and memory.

d) Important with regards to Memory.

e) It is actually toxic to neurons and an excess will kill them.

a. Sometimes brain damage or stroke leads to an excess of Glutamate with many more
brain cells dying because of this than from the original trauma.

f) ALS (Lou Gehrig's disease) results from excessive Glutamate production.

g) Increased alertness or anxiety; due to caffeine may be mainly due to blockage of adenosine
receptors which normally inhibit glutamate release.

h) Monosodium Glutamate (MSG), a major component of soya sauce, has been shown to
destiny nerve cells when fed to young animals

i) Glutamate is considered to be the major mediator of excitatory signals in the mammalian

central nervous system and is involved in most aspects of normal brain function including
cognition, memory and learning.

j) Glutamate does not only mediate a lot of information, but also information which regulates
brain development and information which determines cellular survival, differentiation and
elimination as well as formation and elimination of nerve contacts (synapses). From this it
follows that glutamate has to be present in the right concentrations in the right places for the
right time. Both too much and too little glutamate is harmful. This implies that glutamate is
both essential and highly toxic at the same time.

Synthesis and activation

a) Glutamate is synthesized by glutamine in the Glial cells catalysed by the enzyme

Glutaminase. Some of the glucose that is metabolized by the neuron can be used for
glutamate synthesis.

b) When the action potentials reach the terminals, the calcium channels open and the calcium
ions rush in releasing Glutamate from the vesicles.

c) The diffused glutamate act on particular receptors associated with sodium and potassium
channel. The channels open briefly and sodium rushes in.

d) The diffused glutamate is inactivated by re uptake into pre synaptic terminal by a process
called endocytosis.

Role in brain injury

i. Glutamate is basically excitatory in nature. It is toxic to neurons and if it is

supplied in excess it will kill the neurons.
ii. Brain injury refers to any damage to the brain regardless of age of onset.
iii. When there is a brain damage or stroke it may lead to excess of glutamate which
leads to death of more cells compared to the original trauma.
iv. Reduced glutamate action will lead to memory loss in patients with brain injury.

Amyotrophic Lateral Sclerosis (ALS) Lou Gehrig's Disease

ALS is widely known as Lou Gehrig's disease.

ALS is a degenerative neuromuscular disease that quickly progresses and destroys nerve cells
in the brain and spinal cord. This rapid destruction soon begins to affect motor skills and
basic movement while preserving the mind and the ability to see, hear, touch, feel, and taste.

The most common cause of deal among ALS patients is respiratory failure or pulmonary
infection when to nerve damage eventually affects the muscles that control breathing. The
average survival time after diagnosis with ALS is three to five years
About 75% of people contacting the disease experience "limb onset" ALS i.e. first symptoms
in the arms (upper limb", not to be confused with "upper motor neuron"? or legs ('lower
limb", not to be confused with power motor neuron). Patients with the leg onset for may
experience awkwardness when walking or running or notice that they are tripping or
stumbling, often with a "dropped foot which drags along the ground.

Arm onset patients may experience difficulty with tasks requiring manual dexterity such as
buttoning a shirt, turning a key in a lock. Occasionally, the symptoms remain confined to one
limb for a long period of time or for the whole course of the illness; this is known as
monomclic amyotrophy.

About 25% of cases are "bulbar onset" ALS. These patients fist notice difficulty speaking
clearly or swallowing. Speech may become slurred, nasal in character, or quieter. Other
symptoms include difficulty swallowing, and loss of tongue mobility. A smaller proportion of
patients experience "respiratory onset" ALS where the intercostal muscles that support
breathing are affected fist.

A small percentage of patients go on to develop frontotemporal dementia characterized by

profound personality changes; this is more common among those with a family history of
dementia. A larger proportion of patients experience mild problems with word-generation,
attention, or decision-making. Cognitive function may be affected as part of the disease
process or could be related to poor breathing at night (nocturnal hypoventilation). Health care
professionals need to explain the course of the disease and describe available treatment
options so that patients can make informed decisions in advance.

Regardless of the part of the body first affected by the disease, muscle weakness and atrophy
spread to other parts of the body as the disease progresses. Patients experience increasing
difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria).
Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and
exaggerated reflexes (hyperreflexia) including an overactive gag reflex.

An abnormal reflex commonly called Babinski's sign (the big toe extends upward and other
toes spread out) also indicates upper motor neuron damage. Symptoms of lower motor neuron
degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of
muscles that can be seen under the skin (fasciculation). Around 15 45% of patients
experience pseudobulbar affect, also known as "emotional libility", which consists of
uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor
neurons resulting in exaggeration of motor expressions of emotion.