Neurotransmitter (NTs)

Department of Physiology
School of Medicine
University of Sumatera Utara
 Introduction:
• The Nervous System is incredibly
complex and contains many
important chemical messengers
called neurotransmitters
• Neurotransmitters are amino
acid based molecules that
relay signals between major
systems of the body.
Neurotransmitters define our
moods, actions, and health
Introduction:
• The importance of them
transcends their role in the
brain. They act as messengers
between the: immune,
endocrine, digestive, and
nervous system.
• They are present throughout
the body and required for
proper brain and body
functions. The brain uses
neurotransmitters to tell your
heart to beat, your lungs to
breathe, and your stomach to
digest
Introduction:
• Neurotransmitters are also
necessary for memory and
thinking, feeling, sleeping,
and your energy.
• Scientific literature has
established the link
between neurotransmitter
imbalances and clinical
symptoms
Some symptoms of Neurotransmitter
Imbalance
• Stress, anxiety, mood swings, depression,
irritability, agitation, apathy, panic attacks,
difficulty concentrating, developmental
delays, attention issues, memory decline,
sleep disturbances, headaches, weight
issues, food (carbohydrate) cravings,
fatigue, addiction, decreased sex drive,
hormonal imbalance & PMS, digestive
troubles, autism, and immune system
problems
Neurotransmitter Imbalance
The synthesis of neurotransmitters
The synthesis of neurotransmitters
 Functional Classification of
Neurotransmitters (NTs)
A. Based on effects
– excitatory – cause depolarization (glutamate)
– inhibitory – cause hyperpolarization (GABA)
– effect of some depends on postsynaptic
membrane receptors
• ACh and NE have different receptor types – some
that cause excitation and other types that causes
inhibition
B. Based on mechanism of action
– direct (channel-linked receptors)
– indirect (G protein-linked receptors = second
messenger system)
 Modes of Action: Direct Action
• excitatory examples:
aspartate, acetylcholine
(ACh), glutamate, ATP
*open Na+/K+, Ca2+
channels leading to
• open ion channels depolarization
• immediate and localized • inhibitory examples:
action gamma aminobutyric acid
• action depends on binding (GABA), glycine
of NT to receptors followed *open Cl- or K+ channels
by channel activation, ion leading to
influx and membrane hyperpolarization
potential changes
Modes of Action: Indirect Action
• slower, longer-lasting effects
• work through second messengers
– binding of NT with receptor activates G
protein in membrane which works through
cyclic AMP (cAMP = second messenger) to:
• regulate ion channels (open or close)
• activate kinase enzymes within cytoplasm
(activate proteins in cytoplasm)
 Modes of Action: Indirect Action
Examples
• Biogenic amines (dopamine, norepinephrine, epinephrine)
• Peptides (endorphins, dynorphins, substance P)
• ACh (at muscarinic receptors)
Structural Classes of Neurotransmitters

• Classified according to chemical

structure:
– Acetylcholine (ACh)
– Biogenic Amines
– Amino Acids
– Peptides
– Novel Messengers
 Acetylcholine (ACh)
• first NT to be discovered
• excitatory to skeletal muscles
• excitatory/inhibitory to viscera
• found in CNS and PNS (NMJ with skeletal
muscle, NEJ for parasympathetic nervous
system)
• formed from acetyl-CoA and choline
 Acetylcholine (ACh)
• degraded by acetylcholinesterase (AChE)
• Myasthenia gravis - autoimmune disorder
of skeletal muscle ACh receptors
• Alzheimer’s disease - decreased ACh level
in brain that ultimately results in mental
deterioration
 Biogenic Amines

• synthesized from amino acid tyrosine

• found in CNS and PNS
– catecholamines
• norepinephrine [NE], epinephrine, dopamine,
• excitatory or inhibitory
– indolamines
• seratonin and histamine
• generally inhibitory
 Biogenic Amines
• play role in emotional behavior and help
regulate biological clock; norepinephrine
is main NT of sympathetic division of ANS
• schizophrenia - overproduction of
dopamine
• Parkinson’s disease - deficient dopamine
in basal ganglia
Amino Acids & Peptides
• Amino Acids
– GABA = gamma amino butyric acid (principal
inhibitory NT in brain),
– glycine (generally inhibitory NT, in spinal cord),
– glutamate (CNS, excitatory)
• Peptides (Neuropeptides)
– strings of amino acids produced in CNS and
PNS:
• endorphins and enkephalins (natural opiates)
• substance P (mediator of pain signals)
– some also produced by nonneural tissues (e.g.,
cells of GI tract - somatostatin, cholecystokinin,
vasoactive intestinal peptide [VIP])
Novel Messengers

Neurotransmitters that don’t fit other

categories
• NO = nitric oxide
– involved in long-term synaptic potentiation
(learning and memory)
– relaxation of intestinal smooth muscles
– responsible for brain damage in stroke
patients
Novel Messengers
Neurotransmitters that don’t fit other
categories
• ATP = adenosine triphosphate
– promotes synthesis and uptake of other NTs in
CNS and PNS
• CO = carbon monoxide
– enhances neurotransmission in some circuits
involved in logic
– regulator of cyclic GMP (second messenger)
 Termination of NT Effects
1. removal from cleft by reuptake
into astrocytes or presynaptic
membrane (e.g., norepinephrine)
2. degradation of NT by enzymes
present in postsynaptic membrane
or synaptic cleft
• e.g., acetylcholine [ACh] degraded
by the enzyme acetylcholinesterase -
[AChE]
3. diffusion away from cleft
Causes Neurotransmitters to be out of
balance
• chronic stress,
• poor dietary habits,
• neurotoxins,
• genetics.
Some symptoms of Neurotransmitter
Imbalance ; chronic stress
• the primary contributor to
neurotransmitter imbalance. Stress,
both emotional and physical, can
cause neurons to use up large
amounts of neurotransmitters to help
us cope with the situation
• Chronic daily stress, from a busy
career, a stressed relationship, or a
bacterial or viral infection, will tax the
nervous system, and over time,
deplete neurotransmitter supplies
Some symptoms of Neurotransmitter
Imbalance; poor dietary habits
• Diets with insufficient proteins or
too many high glycemic
carbohydrates will increase
excretion of neurotransmitters
• Also, diets low in Omega-3 fatty
acids will lead to poor neuron
function because our brain cell
membranes are composed
primarily of lipids and Omega-3
fats help to stabilize these
membranes
Some symptoms of Neurotransmitter
Imbalance; neurotoxins

There are a vast amount of

environmental toxins, not to
mention the use of alcohol,
nicotine, and caffeine that also
affect brain chemistry and nervous
system health.
Some symptoms of Neurotransmitter
Imbalance; genetics

Some individuals are metabolically

predisposed to neurotransmitter
deficiencies or excesses. Certain
health conditions, such as depression
and attention deficit/hyperactivity
disorder, are found to run in families