Nervous system Flashcards
The nervous system
The nervous system is the major controlling, regulatory, and communicating system in the body.
- The centre of activity that includes sensation, perception, thought, language, learning, memory and movement initiation.
The nervous system composed of
It is composed of the central (CNS) and peripheral nervous system (PNS), made of a complex network of neurons, and neurotransmitters (NTs), which chemically regulate activity between nerves.
- Mental experience / ‘well-being’ is highly influenced by ‘environment’ ― early experiences, belonging, self esteem, social and situational factors
Key factors affecting nervous system health
- Lifestyle ― environment and our response to it.
- Nerve cell structure and function ― cell membrane integrity via EFAs, phospholipids, myelin, antioxidants, removal of toxins, minerals.
- Hormonal and immune ― oestrogen, testosterone, thyroxine, cortisol, adrenaline, cytokines (inflammation), neurotrophic factors.
- Energy ― relies on a steady flow of glucose and rich in mitochondria.
- Gastrointestinal health ― the ‘second brain’…
Gut-brain axis (GBA)
Gut-brain axis (GBA) = bidirectional communication between the central and enteric nervous system.
- Vagus nerve connects GIT and brain, and contains 80% afferent (sensory) and 20% efferent fibres.
- Gut microbiota play a key role in supporting health of this axis. Dysbiosis can result in extra-intestinal disorders, including nervous and mental health disorders
Gut microbes interact with the GBA in different ways,
- Modulating NT production ― e.g., serotonin which functions as a key NT in the GBA at both its terminals.
- Bacterial metabolites ― e.g., SCFAs support the intestinal barrier, mucosal serotonin release and influence memory and learning processes.
- Modulation of afferent sensory nerves ― e.g., L. reuteri has been shown to enhance neuron excitability, modulating gut motility and pain perception.
- BDNF production ― gut microbiota can modulate BDNF function in the CNS via changes in NT function or by changes in brain SCFAs
Gut barrier function is a key influence on the GBA
- Diet-induced changes in the gut microbiome can lead to a compromised mucus layer, allowing access of luminal microbes to extensions of dendritic cells, resulting in activation of these cells by both pathogens and commensals.
- This local immune activation can lead to ↑ permeability of the tight junctions that further compromises the intestinal barrier.
- This can result in ‘metabolic endotoxemia’, where immune activation in different organs occurs, including the brain.
- Elevated levels of LPS have been associated with neuroinflammation and conditions such as depression
Key factors influencing general nervous function
- Inflammation, oxidative stress, toxic load: E.g., infection, environmental toxins, glycaemic variability, obesity, ↑ intestinal permeability, stress (↑ glucocorticoids), ageing (↑ exposure to cellular stressors), nutritional factors (high sugar, damaged fats, processed foods; low antioxidant-rich foods and omega-3s.
- Decreased expression of neurotrophic factors such as BDNF and nerve growth factor (NGF). Influences include physical and psychological stress, ageing, lack of physical activity.
- Mitochondrial changes: Relate to inflammation and oxidative stress, reduced neurotrophic factors, ageing, nutritional deficits
Neurotransmitters (NTs)
Neurotransmitters (NTs) = chemical messengers released from a pre-synaptic terminal, causing an excitatory or inhibitory effect on the post-synaptic cell.
NT imbalances are the result of an underlying cause, and are often associated with multifactorial issues, such as inadequate nutrition, high stress, toxicity, SNPs, poor digestive health, drug use, etc
* NT synthesis is from specific substrates (e.g., amino acids) using nutritional co-factors (e.g., vitamin B6).
- Methylation ― Methyl folate for biopterin (BH4 ― co-factor for serotonin and dopamine). SAMe (methyl folate and B12) for melatonin and adrenaline
Neurotransmitter balance
Neurotransmitter balance ― NTs need to be inactivated and removed via enzyme breakdown, diffusion or reabsorption. Reuptake transporters are important mechanisms (targeted by e.g., SSRIs). Key enzymes include:
- Monoamine oxidase (MAO) ― breaks down monoamines: serotonin, adrenaline, noradrenaline and dopamine.
- Catechol-O-methyl transferase (COMT) ― breaks down adrenaline, noradrenaline and dopamine using a methyl group from SAMe. SNP rs4680 (G472A) A allele associated with reduced activity.
Serotonin (5-hydroxytryptamine or 5-HT)
Serotonin (5-hydroxytryptamine or 5-HT) = a monoamine NT produced from tryptophan.
- Produced by: Enterochromaffin cells and bacteria in the GIT (95%) and CNS. Tryptophan and 5HTP cross the BBB.
- Functions: GI signalling molecule (motility patterns and epithelial secretions incl. mucus), mood, appetite, sleep (melatonin synthesis), blood clotting.
- Organic acid testing: 5-Hydroxyindolacetic acid (5-HIAA) is a metabolite of serotonin and acts as an indicator of serotonin levels
Low serotonin ― causes / risk factors
Low serotonin ― causes / risk factors:
- Insufficient nutrient status ― i.e., tryptophan and cofactors (e.g., zinc, iron, magnesium, folate, B6 etc.)
- Chronic stress ― hyper-secretion of ACTH and cortisol may alter chaperone proteins which maintain 5HT receptor integrity, reducing 5HT uptake.
- Negative outlook / thinking; a sense of lack of purpose / goals; financial problems, problems at work etc.
- GI dysbiosis ― can impact tryptophan metabolism and gut serotonin production which in turn can both impact brain serotonin metabolism.
- Poor digestive health (see GI 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 ― e.g., arsenic disrupts serotonin metabolism; linked to mood disorders, cognitive decline and can induce neuronal death. Mercury inhibits serotonin receptor binding.
- Sex hormone imbalances (see women’s health) e.g., low oestrogen, as oestrogen normally ↑ tryptophan hydroxylase and inhibits MAO
Low serotonin ―‘tryptophan steal’
- Tryptophan can be metabolised by the kynurenine pathway. Enzyme shunts tryptophan IDO 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.
Low serotonin ― key SNPs
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
Glutamate = a major excitatory NT that Glutamine plays a role in memory and learning
Excess glutamate: Linked to neuronal injury and neurodegenerative diseases, e.g., Alzheimer’s, MS, epilepsy. GABA increases BDNF levels (BDNF is neuroprotective)
GABA deficiency ― key SNPs:
Dopamine imbalances ― key SNPs
Key neurotransmitter summary:
