Serotonin, GABA, Dopamine ... Flashcards
Serotonin (5-
hydroxytryptamine or 5 -HT)
A monoamine NT produced from tryptophan.
Serotonin production
Produced by: Enterochromaffin cells and bacteria in the GIT (95%) and CNS.
Tryptophan and 5HTP cross the BBB.
Serotonin Functions
GI signalling molecule (motility patterns and epithelial secretions incl. mucus), mood, appetite, sleep (melatonin synthesis), blood
Low serotonin
causes / risk factors:
- Insufficient nutrient status i.e., tryptophan and cofactors
- Chronic stress
- Negative outlook / thinking; a sense of lack of purpose / goals; financial problems, problems at work
- GI dysbiosis
- Poor digestive health
- Lack of sunlight in periods of darkness more serotonin is used to synthesise melatonin.
- Caffeine inhibits tryptophan hydroxylase.
- Long term alcohol use shown to lower 5 HT.
- Being sedentary, exercise increases 5 HT.
- Statin use chronic cholesterol depletion using statins impairs the function and dynamics of serotonin 1A receptors.
- Heavy metals
- Sex hormone imbalances
Low serotonin ―‘tryptophan steal’
- Tryptophan can be metabolised by the kynurenine pathway. Enzyme shunts tryptophan to produce NAD+ and ATP at expense of serotonin. Upregulated by stress/inflammation
- Quinolinic acid by product excitotoxin (↑ glutamate), hinders neuronal function, causes cell death. Linked to mood disorders and neurodegenerative diseases.
- Gut microbial tryptophan metabolism can impact kynurenine pathway, so dysbiosis increases.
- Catechins, ECCG, curcumin, pomegranate, garlic, saffron, broccoli sprouts and exercise reduce quinolinic acid neurotoxicity.
Key Low Serotonin SNPs
TPH1
TPH2
FKBP5
5-HTT
5-HT1 & 2AIFNG
TNF
IFNG
MAO
VDR
Low serotonin is associated with
- Mood disorders, anxiety disorders, panic disorders, insomnia, anger, discontentment, eating disorders, OCD, alcohol / substance abuse / addictions.
- IBS and functional constipation; migraines.
Glutamate and GABA
Glutamate = a major excitatory NT that plays a role in memory and learning.
Gamma aminobutyric acid (GABA) = an inhibitory NT.
* They have a Yin Yang relationship
* Excess glutamate: Linked to neuronal injury and neurodegenerative diseases, e.g., Alzheimer’s, MS, epilepsy.
GABA increases BDNF levels (BDNF is neuroprotective).
* GABA deficiency signs and symptoms: Anxiety, insomnia, alcohol craving, panic attacks, palpitations, cold or clammy hands, seizures, carbohydrate cravings, tinnitus.
GABA deficiency
causes / risk factors:
- Alcohol inhibits GAD.
- Co factor deficiencies e.g., vitamin B6, magnesium etc.
- Dysbiosis intestinal bacteria including several strains of Lactobacillus and Bifidobacterium synthesise GABA and influence Vagus activity.
- Chronic stress can reduce GABA activity, possibly through decreased expression of GAD and GABA receptor subunits.
- Also consider limited exercise ; impaired digestion / absorption.
GABA deficiency Key SNPs
BABRA1
GAD
ALPL
Dopamine
Dopamine (DA) = one of the catecholamines (with adrenaline and noradrenaline)
Dopamine Functions
Motor control, curiosity, working memory, cognition. Reward seeking behaviour, motivation; linked to addiction.
* Also acts as a (neuro) hormone released by hypothalamus to inhibit prolactin.
Dopamine depletion
Produces characteristic symptoms of Parkinson’s, e.g., rigidity, tremors, bradykinesia. –
Levodopa, a Parkinson’s drug, crosses the BBB and readily converts to DA.
– B6 is contraindicated to patients on L dopa as it converts it to DA which does not cross the BBB (losing its effect).
Dopamine imbalances
Low levels may be associated with anxiety / depression, low libido and restless leg syndrome.
Elevated levels have been associated with OCD and hyperactivity.
Dopamine imbalances
causes / risk factors
- Insufficient dietary intake of phenylalanine / tyrosine and co factors, e.g., B6, folate, iron, etc. Also consider poor digestion / absorption.
- Chronic stress increases adrenaline (SNS), reducing DA.
- Sleep deprivation downregulates DA receptors.
- High sugar diets.
- Recreational drug use (e.g., cocaine)
- Poor gut health and dysbiosis about 50% of DA is produced in the GIT by enteric neurons, epithelial cells and bacteria, where it normally supports GI motility.
- High saturated fat can alter DA related gene expression.
NT Summary
