10a. Nervous System - Intro Flashcards

1
Q

What is the nervous system made up of?

A

Central
Peripheral

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2
Q

What are the key factors affecting NS health?

A

Lifestyle
Nerve cell structure and function
Hormonal and immune
Energy
GI health

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3
Q

What can affect nerve cell structure and function?

A

Cell membrane integrity via EFAs
Myelin
AOs
Minerals
Removal of toxins

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4
Q

How can hormonal and immune affect NS health?

A

Oestrogen
Testosterone
Thyroxine
Cortisol
Adrenaline
Cytokines
Neurotrophic factors

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5
Q

What is the gut brain axis?

A

Bidirectional communication between the central and enteric NS

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6
Q

What connects the gut and brain in the NS?

A

Vagus nerve

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7
Q

What is the Vagus nerve made up of?

A

80% afferent fibres
20% efferent fibres

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8
Q

How do gut microbes interact with the GBA?

A

Modulates NT production e.g. serotonin
Bacterial metabolites e.g. SCFAs support intestinal barrier
Modulation of afferent sensory nerves
BDNF production

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9
Q

How can gut barrier function influence the GBA?

A

Compromised mucosal layer
Activation of pathogens and commensals
Increased permeability of the tight junction
Resulting in metabolic endotoxaemia

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10
Q

What can high levels of LPS be lead to?

A

Neuroinflammation
Depression

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11
Q

What are the key factors influencing general nervous function?

A

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

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12
Q

What are neurotransmitters?

A

Chemical messengers released from a pre-synaptic terminal
Can cause either an inhibitory or excitatory effect on the post-synaptic cell

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13
Q

What can NT imbalances be the result of?

A

Inadequate nutrition
High stress
Poor digestion health
Toxicity
Drug use
SNPs

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14
Q

What substances does NT synthesis require?

A

Amino acids
Co-factors - B6

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15
Q

Why is methylation important for NTs?

A

Methylfolate for biopterin (BH4 - co-factor for serotonin/dopamine)
SAMe for melatonin/adrenaline

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16
Q

How do we get NT balance?

A

Support reuptake mechanisms
Inactivate and remove used NTs
(enzyme breakdown, diffusion, reabsorption)

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17
Q

What are the key enzymes needed for NT breakdown?

A

Monoamine oxidase (MAO) - breaks down serotonin, adrenaline, noradrenaline, dopamine
COMT - breaks down adrenaline, noradrenaline, dopamine using a methyl group from SAMe

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18
Q

What is serotonin?

A

A monoamine NT produced from tryptophan

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19
Q

What is serotonin produced by?

A

Enterochromaffin cells and bacteria in gut
CNS

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20
Q

What are the functions of serotonin?

A

GI signalling - motility patterns, epithelial secretions
Mood
Appetite
Sleep (melatonin synthesis)
Blood clotting

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21
Q

What is an indicator of serotonin levels on an OAT test?

A

5-HIAA
(metabolite of serotonin)

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22
Q

Sequence of tryptophan to melatonin synthesis

A

Tryptophan - 5HTP - Serotonin - N-Acetylserotonin - Melatonin

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23
Q

Food sources for tryptophan

A

Bananas
Turkey/chicken
Legumes
Pulses
Fish
Oats
Pumpkin seeds
Rice

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24
Q

Co-factors for conversion of tryptophan to 5HTP

A

B3, B6
Vit C
Ca
Fe
Zn
D3
5-MTHF

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25
Q

Enzyme for the conversion of tryptophan to 5HTP

A

Tryptophan hydroxylase

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26
Q

Co-factors for conversion of 5HTP to serotonin

A

B6
Mg
Vit C
Zn

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27
Q

Enzyme for the conversion of 5HTP to serotonin

A

Aromatic acid decarboxylase

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28
Q

Co-factor for conversion of serotonin to N-Acetylserotonin

A

Acetyl-CoA
(B5)

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29
Q

Co-factor for conversion of N-Acetylserotonin to melatonin

A

SAMe
(5-MTHF, B12)

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30
Q

Causes and risk factors for low serotonin

A

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

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31
Q

Deficiency in which nutrients can lead to low serotonin

A

Tryptophan
Zn
Fe
Mg
B6
B9

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32
Q

What is the mechanism for chronic stress lowering serotonin?

A

Hyper-secretion of ACTH and cortisol may alter chaperone proteins which maintain 5HT receptor integrity and uptake

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33
Q

What is the mechanism for GI dysbiosis lowering serotonin?

A

Dysbiosis can impact tryptophan metabolism and gut serotonin which in turn can impact brain serotonin metabolism

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34
Q

How can lack of sunlight lower serotonin levels?

A

In periods of darkness, more serotonin is used to synthesise melatonin

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35
Q

How does caffeine lower serotonin levels?

A

Inhibits tryptophan hydroxylase

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36
Q

How does being sedentary lower serotonin levels?

A

Exercise increases serotonin

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37
Q

How does statin use lower serotonin levels?

A

Chronic cholesterol depletion using statins impairs the function and dynamics of serotonin 1A receptors

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38
Q

How can heavy metals lower serotonin levels?

A

Arsenic disrupts serotonin metabolism and can induce neuronal death
Mercury inhibits serotonin receptor binding

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39
Q

How can sex hormone imbalances lower serotonin levels?

A

Low oestrogen can lower the activity of tryptophan hydroxylase

40
Q

What is the tryptophan steal?

A

Enzymes shunt tryptophan to make NAD+ and ATP at the expense of serotonin

41
Q

Which pathway is used to make tryptophan?

A

Kynurenine

42
Q

What can upregulate the tryptophan steal?

A

Stress
Inflammation

43
Q

What is the by-product of the conversion of tryptophan to NAD+ via the kynurenine pathway?

A

Quinolinic acid

44
Q

What does quinolinic acid do?

A

Increases glutamate (excitatory)
Hinders neuronal function
Causes cell death

45
Q

Which conditions is quinolinic acid linked to?

A

Neurodegenerative diseases
Mood disorders

46
Q

Natural solutions to lowering quinolinic acid neurotoxicity

A

Catechins
EGCG
Curcumin
Garlic
Broccoli sprouts
Pomegranate
Saffron

47
Q

Examples of SNPs associated with low serotonin

A

TPH1
TPH2
5-HTT
5-HT1
5-HT2A
MAO-A
VDR

48
Q

What can a SNP on TPH1 result in?

A

Effects peripheral serotonin synthesis
Constipation (if slow)

49
Q

What can a SNP on TPH2 result in?

A

Lower CNS serotonin synthesis

50
Q

What can a SNP on 5-HTT effect?

A

SERT transporters

51
Q

What can a SNP on 5-HT1 and 2A result in?

A

Reduction in the effects of serotonin

52
Q

What can a SNP on MAO-A result in?

A

More enzymatic breakdown and lower serotonin

53
Q

What can a SNP on VDR result in?

A

Lower sensitivity to vit D
Less support for serotonin synthesis

54
Q

Which conditions/disorders is low serotonin associated with?

A

Mood/Anxiety/Panic disorders
Insomnia
Anger
Eating disorders
OCD
Addictions
IBS/constipation
Migraines

55
Q

What is glutamate?

A

Excitatory NT that has a role in memory/learning

56
Q

What is GABA?

A

An inhibitory NT

57
Q

What are the functions of GABA?

A

Sleep
Relaxation

58
Q

Co-factors for the production of GABA

A

B6
Zn
Mg
Vit C

59
Q

Which conditions is excess glutamate associated with?

A

AZD
MS
Epilepsy

60
Q

Signs and symptoms of GABA deficiency

A

Anxiety
Insomnia
Alcohol craving
Carb craving
Panic attacks
Palpitations
Seizures
Tinnitus
Cold or clammy hands

61
Q

Which enzyme converts glutamate to GABA?

A

Glutamate decarboxylase (GAD)

62
Q

Causes and risk factors for a GABA deficiency

A

Alcohol - inhibits GAD
Co-factor deficiencies - B6, Mg, Zn, vit C
Dysbiosis
Chronic stress
Limited exercise
Impaired digestion/absorption

63
Q

How can dysbiosis cause a GABA deficiency?

A

Several strains of Lactobacillus and Bifidobacterium synthesise GABA and influence Vagus nerve activity

64
Q

How can chronic stress reduce GABA activity?

A

Decreased expression of GAD and GABRA2 receptors

65
Q

Key GABA SNPs

A

GABRA2
GAD

66
Q

What does a SNP on GABRA2 do?

A

Lowers sensitivity to GABA - feels like you have less GABA

67
Q

What are people with a GABRA2 SNP likely to do?

A

Misuse alcohol to get the GABA relaxation effect

68
Q

What does a SNP on GAD1 and 2 do?

A

Impacts glutamate to GABA synthesis

69
Q

What are the functions of dopamine?

A

Motor control
Reward seeking
Motivation

70
Q

Which hormone does dopamine inhibit?

A

Prolactin

71
Q

Which test is best for looking at dopamine levels?

A

OAT

72
Q

What is the indicator on an OAT test for dopamine levels?

A

HVA

73
Q

Stages to making dopamine/adrenaline/noradrenaline

A

Phenylalanine - tyrosine - L-dopa - dopamine/adrenaline/noradrenaline

74
Q

Co-factors in the conversion of phenylalanine to dopamine

A

B1, B3, B6
Vit C
Fe
5-MTHF

75
Q

Enzymes needed for the conversion of phenylalanine to dopamine

A

Phenylalanine hydroxylase
Tyrosine hydroxylase

76
Q

Signs of dopamine depletion

A

Rigidity
Tremors
Bradykinesia

77
Q

What is the drug for treating Parkinson’s?

A

Levodopa

78
Q

Which vitamin is contraindicated for anyone on levodopa?

A

B6
(converts levodopa to dopamine but it doesn’t cross BBB, losing its effect)

79
Q

Which food ingredient increases dopamine release?

A

Sugar

80
Q

Which conditions are low levels of dopamine associated with?

A

Anxiety/depression
Low libido
Restless leg syndrome

81
Q

Which conditions are high levels of dopamine associated with?

A

OCD
Hyperactivity

82
Q

Causes and risk factors of dopamine imbalances

A

Insufficient dietary intake of phenylalanine/tyrosine/co-factors
Poor digestion/absorption
Chronic stress - increases adrenaline
Sleep deprivation - downregulates DA receptors
High sugar diets
High saturated fat diets
Recreational drug use
Poor gut health/dysbiosis

83
Q

Why can poor gut health/dysbiosis lead to a dopamine imbalance?

A

50% of dopamine produced in GIT
(enteric neurons, epithelial cells, bacteria)

84
Q

Key SNPs for a dopamine imbalance

A

TH
MTHFR
COMT
MAOB

85
Q

What does a SNP on TH do?

A

Increases TH activity = increased DA
Good for cognition
Bad as could = excess DA

86
Q

What does a SNP on MTHFR do for dopamine?

A

Reduces methylfolate which can impact dopamine synthesis

87
Q

What does a SNP on COMT do for dopamine?

A

Breaks down DA
Fast COMT lowers DA
Slow COMT increases DA

88
Q

What does a SNP on MAOB do for dopamine?

A

Breaks down DA more slowly

89
Q

What is acetylcholine?

A

Major NT in the PSNS
Anti-inflammatory in brain

90
Q

What are the main functions of acetylcholine?

A

Mood
Memory
Learning

91
Q

What is acetylcholine formed from?

A

Acetyl-CoA
Choline (dietary)

92
Q

What can downregulate acetylcholine?

A

Cortisol
(inhibits acetyltransferase)

93
Q

Key food sources of choline

A

Eggs
Chickpeas
Oranges
Cauliflower

94
Q

What are the amino acids needed to produce taurine?

A

Methionine
Cysteine

95
Q

What are the functions of taurine?

A

GABA agonist
Glutamate antagonist

96
Q

What is the co-factor needed to make taurine?

A

B6