Nervous System Flashcards
What is the nervous system?
The controlling, regulatory, communicating system.
Composed of the CNS, PNS and a network of neurons and neurotransmitters
Name 5 things that affect the NS
- Lifestyle (and environment)
- Nerve cell structure and function (cell mem integrity via EFAs, phosphos, myelin, antioxs, removal of toxins)
- Hormonal and Immune (oestrogen, testosterone, thyroxine, cortisol, adrenaline)
- Energy (flow of glucose and mito)
- GI Health
What is the ‘gut-brain axis (GBA)?
Bidirectional comms between the central and enteric NS
The Vagus nerve connects the two and contains 80% afferent (sensory) and 20% efferent fibres.
How do gut microbes interact with the GBA?
- Modulating NT prod. (e.g. serotonin functions in the GBA at both terminals
- Bacterial metabolites (e.g. SCFA support intestinal barrier, mucosal serotonin release and influence memory.
- Modulation of afferent sensory nerves
- BDNF (Brain derived neurotrophic factor) - gut microbiota can modulate BDNF function via CNS.
How does the gut barrier function influence GBA?
- Diet can compromise the mucus layer allowing access of luminal microbes to extensions of dendritic cells by pathogens and commensals.
- This immune activation can lead to increased perm of the tight junctions.
- This can result in metabolic endotoxemia = immune activation.
- High levels of LPS are associated with neuroinflamm/depression.
Name 3 factors influencing general nervous func.
- Inflam, oxidative stress, toxic load (infection, environmental toxins, b/glucose imbalance, obesity, increased intestinal perm, stress, ageing, nut).
- Decreased expression of neurotrophic factors (BDNF and NGF)
- Mito changes (inflam, oxidative stress, ageing, nut def)
What is a neurotransmitter?
Chemical messenger released from a presynaptic terminal, causing an excitatory or inhibitory effect on a postsynaptic cell.
How do you acquire NY synthesis?
From a specific substrate using nutritional co-factors.
How do you balance neurotransmitters?
They need to be inactivated and removed via enzyme breakdown, diffusion or reabsorption.
Reuptake transporters are important mechansims (MAO/COMT)
Name two reuptake transporters and how they work.
MAO: Breaks down monoamines: serotonin, adrenaline, noradrenaline, dopamine
COMT: Breaks down adrenaline, noradrenaline and dopamine using SAMe.
What is serotonin?
A monoamine neurotransmitter produced by tryptophan.
What does serotonin do?
It is a GI signalling molecule for mood, appetite, sleep (melatonin), blood clotting.
What causes low serotonin?
- Insufficient nut status: Tryptophan and cofactors (zinc, iron, mg, folate, B6)
- Chronic stress: Hypersecretion of ACTH and cortisol. This alters proteins which maintain 5HT receptors reducing 5HT uptake.
- Dysbiosis: Can impact tryptophan metabolism and get serotonin prod which impact brain serotonin metabolism.
- Poor dig health
- Lack of sunlight: In periods of darkness, more serotonin is used to synthesise melatonin.
- Caffeine: Inhibits tryptophan hydroxylase
- Long term alcohol use: Reduces 5HT
- Sedentary: Exercise increases 5HT
- Heavy metals e.g. arsenic disrupts serotonin metabolism and mercury inhibits serotonin receptor binding
- Sex hormone imbalances e.g. low oest as oest normally increases tryptophan hydroxylase and inhibits MAO.
What is the ‘Tryptophan Steal’?
This is where tryptophan is metabolised by the kynurenine pathway instead of the 5 HTP pathway so it shunts it to produce NAD and ATP at the expense of serotonin.
This upregs stress because QUINOLINIC ACID (the bi-product of the kynurenine pathway) is an excitotoxin and increases glutamate, hinders neural func and cases cell death.
What reduces quinolinic acid?
ECCG, Green tea, curcumin, poms, garlic and saffron.
Name 5 SNPs that increase the odds of LOW SEROTONIN.
- TPH1 - can result in constipation.
- TPH2 - impacts serotonin synthesis
- 5-HTT - reduces the effects of serotonin (SSRIs target these)
- MAO-A - high activity SNP leads to more enzymatic breakdown and lower sero
- VDR - Lower sensitivity to Vit D= less support for serotonin synthesis.
What is low serotonin associated with?
Mood, anxiety, panic disorders, insomnia, eating disorders, OCD, addictions, IBS, migraines and constipation.
What is GLUTAMATE?
A major excitatory NT that plays a role in memory and learning.
What is GABA?
An inhibitory NT
What happens if you have too much GLUTAMATE?
Linked to neurol injury and neurodegenerative diseases
What happens if you have a GABA deficiency?
Anxiety, insomnia, alcohol cravings, panic attacks, palps, cold/clammy hands, seizures, carb cravings.
What causes GABA def?
- Alcohol (inhibits GAD)
- Cofactor def: B6/MG
- Dysbiosis: Lacto and Bifido synthesise GABA and influence vagus activity
- Chronic stress: can reduce GABA
Name 3 SNPs that contribute to GABA def.?
- GABRA2: Lowers sensitivity to GABA (linked to anxiety and alcohol use)
- GAD (glutamate): Impacts glutamate to GABA conversion.
- ALPL: Degrades B6