10a. Nervous System - Intro Flashcards
What is the nervous system made up of?
Central
Peripheral
What are the key factors affecting NS health?
Lifestyle
Nerve cell structure and function
Hormonal and immune
Energy
GI health
What can affect nerve cell structure and function?
Cell membrane integrity via EFAs
Myelin
AOs
Minerals
Removal of toxins
How can hormonal and immune affect NS health?
Oestrogen
Testosterone
Thyroxine
Cortisol
Adrenaline
Cytokines
Neurotrophic factors
What is the gut brain axis?
Bidirectional communication between the central and enteric NS
What connects the gut and brain in the NS?
Vagus nerve
What is the Vagus nerve made up of?
80% afferent fibres
20% efferent fibres
How do gut microbes interact with the GBA?
Modulates NT production e.g. serotonin
Bacterial metabolites e.g. SCFAs support intestinal barrier
Modulation of afferent sensory nerves
BDNF production
How can gut barrier function influence the GBA?
Compromised mucosal layer
Activation of pathogens and commensals
Increased permeability of the tight junction
Resulting in metabolic endotoxaemia
What can high levels of LPS be lead to?
Neuroinflammation
Depression
What are the key factors influencing general nervous function?
Inflammation
Oxidative stress
Toxic load
Decreased expression of neurotrophic factors e.g. BDNF due to stress, ageing, lack of physical activity
Mitochondrial changes e.g. inflammation, ageing, nutritional deficits
What are neurotransmitters?
Chemical messengers released from a pre-synaptic terminal
Can cause either an inhibitory or excitatory effect on the post-synaptic cell
What can NT imbalances be the result of?
Inadequate nutrition
High stress
Poor digestion health
Toxicity
Drug use
SNPs
What substances does NT synthesis require?
Amino acids
Co-factors - B6
Why is methylation important for NTs?
Methylfolate for biopterin (BH4 - co-factor for serotonin/dopamine)
SAMe for melatonin/adrenaline
How do we get NT balance?
Support reuptake mechanisms
Inactivate and remove used NTs
(enzyme breakdown, diffusion, reabsorption)
What are the key enzymes needed for NT breakdown?
Monoamine oxidase (MAO) - breaks down serotonin, adrenaline, noradrenaline, dopamine
COMT - breaks down adrenaline, noradrenaline, dopamine using a methyl group from SAMe
What is serotonin?
A monoamine NT produced from tryptophan
What is serotonin produced by?
Enterochromaffin cells and bacteria in gut
CNS
What are the functions of serotonin?
GI signalling - motility patterns, epithelial secretions
Mood
Appetite
Sleep (melatonin synthesis)
Blood clotting
What is an indicator of serotonin levels on an OAT test?
5-HIAA
(metabolite of serotonin)
Sequence of tryptophan to melatonin synthesis
Tryptophan - 5HTP - Serotonin - N-Acetylserotonin - Melatonin
Food sources for tryptophan
Bananas
Turkey/chicken
Legumes
Pulses
Fish
Oats
Pumpkin seeds
Rice
Co-factors for conversion of tryptophan to 5HTP
B3, B6
Vit C
Ca
Fe
Zn
D3
5-MTHF
Enzyme for the conversion of tryptophan to 5HTP
Tryptophan hydroxylase
Co-factors for conversion of 5HTP to serotonin
B6
Mg
Vit C
Zn
Enzyme for the conversion of 5HTP to serotonin
Aromatic acid decarboxylase
Co-factor for conversion of serotonin to N-Acetylserotonin
Acetyl-CoA
(B5)
Co-factor for conversion of N-Acetylserotonin to melatonin
SAMe
(5-MTHF, B12)
Causes and risk factors for low serotonin
Insufficient nutrient status
Chronic stress
GI dysbiosis
Poor digestive health
Lack of sunlight
Caffeine
Long-term alcohol use
Being sedentary
Statin use
Heavy metals
Sex hormone imbalances
Deficiency in which nutrients can lead to low serotonin
Tryptophan
Zn
Fe
Mg
B6
B9
What is the mechanism for chronic stress lowering serotonin?
Hyper-secretion of ACTH and cortisol may alter chaperone proteins which maintain 5HT receptor integrity and uptake
What is the mechanism for GI dysbiosis lowering serotonin?
Dysbiosis can impact tryptophan metabolism and gut serotonin which in turn can impact brain serotonin metabolism
How can lack of sunlight lower serotonin levels?
In periods of darkness, more serotonin is used to synthesise melatonin
How does caffeine lower serotonin levels?
Inhibits tryptophan hydroxylase
How does being sedentary lower serotonin levels?
Exercise increases serotonin
How does statin use lower serotonin levels?
Chronic cholesterol depletion using statins impairs the function and dynamics of serotonin 1A receptors
How can heavy metals lower serotonin levels?
Arsenic disrupts serotonin metabolism and can induce neuronal death
Mercury inhibits serotonin receptor binding