serotonin Flashcards
5-HT is an extremely important neurotransmitter that
influences many physiological and behavioral processes… and
is also the target of many drugs
- Fluoxetine (Prozac) and other medications
exert their therapeutic effect by acting on
serotonin system; - Hallucinogenic drugs such as LSD,
psilocybin, MDMA and others mimic
some of the effects of serotonin; - Many ”normal” behaviors appear to
depend on intact serotonin function in the brain
where is 5-HT located
The vast majority of 5-HT is peripheral gut
Peripheral 5-HT controls
gut motility and initiates peristaltic and secretory reflex
Disruptions of brain 5-HT function are
thought to play a significant role in
various psychiatric conditions such as:
Anxiety, substance use & addiction,
mood control, et
Tryptophan
is an essential amino acid, which
means it cannot be synthesized by the
organism. It, therefore, must be obtained via
diet.
Foods that are high in tryptophan:
Oats, bananas, dried dates, milk, yogurt, cottage
cheese, red meat, eggs, fish, poultry, sesame,
chickpeas, sunflower seeds, pumpkin seeds,
peanuts, etc
Tryptophan Hydroxylase
is
the rate-limiting enzyme in serotonin
synthesis
Tryptophan must compete with large, neutral amino
acids to cross the BBB
High-protein, low carbohydrate diet does not increase
brain tryptophan too much competition;
- High-carbohydrate, low-protein diet does enhance brain
levels of tryptophan, and ultimately synthesis of 5-HT
Rate-limiting step
of central 5-HT synthesis is
passage of tryptophan across BBB
Tryptophan hydroxylase comes in 2
forms (at the level of the gene):
- TPH1 – expressed by 5-HT
secreting cells in the gut and
melatonin-secreting cells in the
pineal gland; - TPH2 – expressed by 5-HT
secreting neurons
Tryptophan hydroxylase is
present only in
a small subset of neurons
Raphe
Nuclei.
Tryptophan hydroxylase is
present only in a small
subset of neurons;
These cells are located in a
series of cell groups in the
brainstem, collectively
known has the Raphe
Nuclei
Almost all serotonergic neurons in the CNS are found along the
midline of the brainstem, associated with the
raphe nuclei
Raphe nuclei are divided into
dorsal and median raphe nuclei
Serotonin receptors are a large group of G protein coupled receptor (mostly) and ligand-
gated ion channels found in both the
brain and periphery
5-HT1A
receptors are concentrated
in the hippocampus, septal area,
amygdala, and the dorsal raphe
nuclei
- Reduce cAMP synthesis by
inhibiting adenylyl cyclase; - Increase opening of K+ channels
and membrane hyperpolarization. - Similar activity to D2 and a2
receptors; - Leads to decrease cell firing in post-
synaptic cell (post-synaptic receptor)
or serotonergic neuron itself (auto-
receptor
5-HT2A
receptors are located
throughout the brain, however they
are in large numbers in the
(neo)cortex
Primarily responsible for activating
phosphoinositide 2nd messenger
system.
- Increases Ca2+ influx into
postsynaptic cells;
- Activated protein kinase C (PKC)
Following the release of 5-HT, it is rapidly removed from
the synaptic cleft via the
5-HT reuptake transporter
(SERT)
What happens when we don’t have
enough tryptophan?
SAD
SAD is thought to be caused by
a reduction in sunlight and
may be related to reductions in serotonin (although, nothing
has been proven… yet). Typical SSRI’s can reverse
depressive-like symptoms of SAD.
The Atkins diet
a commercial weight-loss
program that essentially limits (severely)
the amount of carbohydrates one
consumes.
We know, however, that low levels of
central serotonin are strongly associated
with levels of
depression
