Module 10 Nervous System PDF

Key Conditions and Pathophysiology: 1. Depression: o Characterized by persistent sadness, low self-esteem, anxiety, and loss of interest. o Causes include neurotransmitter imbalances (e.g., serotonin), nutrient deficiencies (omega-3, B-vitamins), gut dys...

Key Conditions and Pathophysiology: 1. Depression: o Characterized by persistent sadness, low self-esteem, anxiety, and loss of interest. o Causes include neurotransmitter imbalances (e.g., serotonin), nutrient deficiencies (omega-3, B-vitamins), gut dysbiosis, and chronic inflammation. o Nutrients/Supplements: ▪ Omega-3s (EPA/DHA): 1000 mg daily. ▪ B Complex: 50-150 mg/day. ▪ 5-HTP: 100-300 mg daily. ▪ Phosphatidylserine: 100 mg 3 times/day. ▪ Saffron: 30 mg 2 times/day. 2. Bipolar Depression: o Alternating periods of depression and elevated mood. o Focus on nutrient-rich diet, high in omega-3, folate, and adequate protein. o Nutrients/Supplements: ▪ Vitamin C: 500-2000 mg/day. ▪ Vitamin B6 (P5P): 20-150 mg/day. ▪ Magnesium: 100-600 mg. ▪ 5-HTP: 50-100 mg. 3. Anxiety: o Includes generalized anxiety, panic, and post-traumatic stress, often linked to stress, inflammation, gut dysbiosis, and nutrient deficiencies. o Nutrients/Supplements: ▪ Magnesium: 200-400 mg/day. ▪ Zinc: 15-60 mg/day. ▪ B Complex: 50-150 mg/day. ▪ Vitamin C: 500 mg 3 times/day. ▪ Theanine: 50-200 mg/day. 4. Insomnia: o Difficulty falling or staying asleep, often related to cortisol/adrenaline imbalances or melatonin issues. o Nutrients/Supplements: ▪ Magnesium: 200-400 mg. ▪ Lemon balm: 300-600 mg. ▪ Theanine: 50-200 mg. ▪ 5-HTP: 50-300 mg. 5. Migraine: o Recurrent headaches triggered by stress, inflammation, histamine, or nutrient deficiencies. o Nutrients/Supplements: ▪ Magnesium: 200-400 mg/day. ▪ Vitamin B6: 50-100 mg/day. ▪ 5-HTP: 100-200 mg twice/day. ▪ Ginger: 400 mg 3 times/day. ▪ Feverfew: 300 mg daily. These supplements support the nervous system by balancing neurotransmitters, reducing inflammation, and promoting neuroprotection. Key SNPs (Single Nucleotide Polymorphisms) Related to Nervous System Health: 1. TPH1 & TPH2 (Tryptophan Hydroxylase 1 & 2): o TPH1: Involved in peripheral serotonin synthesis (e.g., in the gut). SNPs here can lead to slower serotonin production and issues like constipation. o TPH2: Responsible for central nervous system (CNS) serotonin production. SNPs may reduce serotonin levels, affecting mood and cognition. 2. FKBP5: o Affects cortisol regulation, influencing the kynurenine pathway (which depletes tryptophan for serotonin synthesis). SNPs here can exacerbate stress and inflammation. 3. 5-HTT (SERT/SLC6A4): o Codes for serotonin transporters. SNPs can decrease serotonin reuptake, affecting mood and increasing risks of depression and anxiety. 4. COMT (Catechol-O-Methyl Transferase): o Breaks down dopamine, adrenaline, and noradrenaline using methylation. Fast COMT variants lead to lower dopamine levels, which can affect mood and cognitive function. 5. MAO-A (Monoamine Oxidase-A): o Breaks down serotonin, dopamine, and other neurotransmitters. High-activity SNPs can cause excessive breakdown of serotonin, leading to mood disorders like depression. 6. MTHFR (Methylenetetrahydrofolate Reductase): o Supports methylation and neurotransmitter synthesis. SNPs can reduce methyl-folate availability, impacting serotonin and dopamine synthesis, potentially causing mood disorders. 7. GABRA2 (GABA Receptor A2): o SNPs here reduce GABA receptor sensitivity, leading to anxiety and increased alcohol consumption (due to GABA-like effects of alcohol). 8. SLC6A3/DAT (Dopamine Transporter): o Involved in dopamine reuptake. SNPs that increase transporter activity lower dopamine availability, increasing the risk of addiction and cognitive decline. 9. DRD2/DRD4 (Dopamine Receptor): o SNPs here increase susceptibility to addictive behaviors and impulsiveness due to altered dopamine receptor activity. 10. ALPL (Alkaline Phosphatase): o Breaks down vitamin B6, a cofactor for GABA synthesis. Faster degradation of B6 results in lower GABA, contributing to anxiety. Key Gut Bacteria and Their Role in Nervous System Health: 1. Lactobacillus and Bifidobacterium Species: o These bacteria are involved in the synthesis of GABA, an inhibitory neurotransmitter that has calming effects and helps reduce anxiety. They also influence the Vagus nerve, enhancing communication between the gut and the brain (gut-brain axis). 2. Lactobacillus reuteri:  o This strain enhances neuron excitability and modulates gut motility and pain perception. It plays a role in maintaining healthy Vagus nerve signaling. 3. Bifidobacterium infantis and Bifidobacterium longum: o These strains lower histamine levels and reduce inflammation, which helps in managing symptoms of anxiety and depression. 4. Bifidobacterium bifidum: o Important for reducing intestinal permeability and preventing metabolic endotoxemia, which can lead to neuroinflammation and mood disorders. 5. Coprococcus and Faecalibacterium: o Butyrate-producing bacteria that are essential for maintaining a healthy gut barrier. They have been linked to lower levels of depression by promoting anti-inflammatory effects in the gut. 6. Helicobacter pylori: o Associated with elevated calcitonin gene-related peptide (CGRP), which can contribute to migraine development due to neurogenic inflammation. 7. Lactobacillus rhamnosus: o Known to modulate the gut-brain axis and reduce anxiety by increasing GABA production and improving communication via the Vagus nerve. 8. Gut Microbiota & Brain-Derived Neurotrophic Factor (BDNF): o Gut microbiota influence the production of BDNF, which is crucial for memory, learning, and overall brain health. Dysbiosis can lead to lower BDNF levels and cognitive impairments. Importance: Gut bacteria play a vital role in modulating neurotransmitter production, including serotonin, GABA, and dopamine, impacting mood, cognition, and stress responses. Maintaining a healthy and diverse gut microbiota helps regulate inflammation, which is closely linked to mood disorders like depression and anxiety. SNPs provide insight into individual genetic predispositions for neurotransmitter imbalances, stress responses, and risk for conditions like anxiety, depression, and addiction. Understanding these SNPs helps in personalized nutrition and lifestyle interventions. Tryptophan Pathway to Melatonin: 1. Tryptophan to 5-HTP (5-Hydroxytryptophan): o The amino acid tryptophan is first converted into 5-HTP via the enzyme tryptophan hydroxylase (TPH). This is the rate-limiting step in serotonin synthesis. o Cofactors: This step requires iron and tetrahydrobiopterin (BH4), which is derived from methylation processes supported by folate (B9), B6, and B12. 2. 5-HTP to Serotonin (5-HT): o 5-HTP is converted into serotonin (5-HT) by the enzyme aromatic amino acid decarboxylase (AADC).  oCofactors: Vitamin B6 is required for this conversion. 3. Serotonin to N-Acetylserotonin: o In the pineal gland, serotonin is acetylated by the enzyme serotonin-N- acetyltransferase (AANAT) to form N-acetylserotonin. o Cofactors: This step requires acetyl-CoA, which is supported by vitamin B5 (pantothenic acid). 4. N-Acetylserotonin to Melatonin: o Finally, N-acetylserotonin is methylated by hydroxyindole-O- methyltransferase (HIOMT) (also known as acetylserotonin-O- methyltransferase (ASMT)) to form melatonin. o Cofactors: This reaction requires SAMe (S-Adenosyl methionine), which is generated from methylation processes involving B12 and folate (5-MTHF). Melatonin, synthesized in response to darkness, regulates the circadian rhythm and sleep- wake cycle. Tryptophan Steal: The tryptophan steal occurs when tryptophan, instead of being converted to serotonin (and eventually melatonin), is diverted into the kynurenine pathway. This process happens under conditions of stress or inflammation and results in decreased availability of tryptophan for serotonin and melatonin production. Kynurenine Pathway: o Under stress, the enzyme indoleamine 2,3-dioxygenase (IDO) is upregulated by inflammatory cytokines (e.g., TNF-alpha, IFN-gamma). This enzyme converts tryptophan into kynurenine instead of 5-HTP. o Kynurenine is further metabolized into quinolinic acid, a neurotoxin that increases glutamate (an excitatory neurotransmitter) and contributes to neuroinflammation and mood disorders. The tryptophan steal is particularly problematic in people with chronic stress, autoimmune conditions, or inflammatory disorders, as it reduces serotonin and melatonin production, leading to mood imbalances (e.g., depression, anxiety), sleep disturbances, and cognitive issues. Key Enzymes Involved in the Tryptophan Pathway: 1. Tryptophan Hydroxylase (TPH1 and TPH2): o TPH1 is responsible for serotonin synthesis in peripheral tissues (e.g., gut). o TPH2 is responsible for serotonin production in the brain. o Cofactors: Requires BH4, iron, and B6. 2. Aromatic Amino Acid Decarboxylase (AADC): o Converts 5-HTP into serotonin. o Cofactors: Vitamin B6. 3. Serotonin-N-Acetyltransferase (AANAT):  o Converts serotonin to N-acetylserotonin. o Cofactors: Acetyl-CoA (dependent on B5). 4. Acetylserotonin-O-Methyltransferase (ASMT/HIOMT): o Converts N-acetylserotonin into melatonin. o Cofactors: SAMe (dependent on B12 and folate). 5. Indoleamine 2,3-Dioxygenase (IDO): o Catalyzes the conversion of tryptophan into kynurenine, diverting it from serotonin synthesis. o Upregulated by inflammatory cytokines during periods of stress or immune activation. Key SNPs (Single Nucleotide Polymorphisms) Related to the Tryptophan Pathway: 1. TPH1 & TPH2 SNPs: o TPH1 SNPs (Tryptophan Hydroxylase 1): Affect serotonin synthesis in peripheral tissues (e.g., gut). A slower variant can result in reduced serotonin production, which may lead to constipation and other gut-related issues. o TPH2 SNPs (Tryptophan Hydroxylase 2): Affect CNS serotonin synthesis. A slower variant can result in decreased serotonin levels in the brain, leading to depression or anxiety. 2. FKBP5 SNP: o Increases cortisol dysregulation, which leads to upregulation of the kynurenine pathway, diverting tryptophan from serotonin synthesis. This SNP is often linked to stress-induced depression. 3. 5-HTT/SERT (SLC6A4): o This gene encodes the serotonin transporter, which is responsible for serotonin reuptake. SNPs here can affect serotonin availability and are linked to increased risk of depression and anxiety. 4. MAO-A SNP: o This gene codes for monoamine oxidase-A, the enzyme that breaks down serotonin. SNPs can result in either high activity (leading to lower serotonin levels) or low activity (leading to higher serotonin levels). High activity SNPs are associated with depression. 5. MTHFR SNP: o This gene affects the methylation cycle by converting folate into its active form (5-MTHF). SNPs here reduce the availability of 5-MTHF, impacting the production of BH4 (a cofactor for serotonin synthesis) and SAMe (needed for melatonin synthesis). MTHFR mutations are linked to depression and mood disorders due to impaired serotonin and melatonin synthesis. In summary, the tryptophan pathway is crucial for the synthesis of serotonin and melatonin, both of which are essential for mood regulation and sleep. SNPs affecting key enzymes in this pathway can lead to significant neurotransmitter imbalances, contributing to conditions like depression, anxiety, and sleep disturbances. Additionally, the tryptophan steal diverts tryptophan to inflammatory processes, further depleting serotonin and melatonin levels under stress. Flashcard 1: Question: What are the two main divisions of the nervous system? Answer: The central nervous system (CNS) and the peripheral nervous system (PNS). Flashcard 2: Question: What is the primary neurotransmitter involved in mood regulation? Answer: Serotonin. Flashcard 3: Question: What nutrient is essential for serotonin synthesis? Answer: Tryptophan. Flashcard 4: Question: What is the role of omega-3 fatty acids in nervous system health? Answer: They maintain neuronal membrane fluidity, support neurotransmitter function, and reduce inflammation. Flashcard 5: Question: Which neurotransmitter is known as the primary inhibitory neurotransmitter? Answer: GABA (Gamma-aminobutyric acid). Flashcard 6: Question: What nutrient supports GABA production and has calming effects? Answer: Magnesium. Flashcard 7: Question: What neurotransmitter is associated with the "reward" system and motivation? Answer: Dopamine. Flashcard 8: Question: What amino acid is a precursor to dopamine? Answer: Tyrosine. Flashcard 9: Question: Which vitamin is a key co-factor in dopamine production? Answer: Vitamin B6. Flashcard 10: Question: What neurotransmitter imbalance is commonly associated with depression? Answer: Low serotonin levels. Flashcard 11: Question: What natural supplement can help boost serotonin levels in depression? Answer: 5-HTP (5-Hydroxytryptophan). Flashcard 12: Question: What is the gut-brain axis? Answer: It is the bidirectional communication network between the gut and the brain, involving neurotransmitters and immune signals. Flashcard 13: Question: How does chronic stress impact neurotransmitter levels? Answer: Chronic stress increases cortisol, which can reduce serotonin and GABA levels, leading to mood disorders. Flashcard 14: Question: Which herb is known for its mood-lifting effects and often used to treat depression? Answer: St. John's Wort (Hypericum perforatum). Flashcard 15: Question: What is the recommended daily dose of omega-3 for supporting mental health? Answer: At least 1000 mg of combined EPA and DHA. Flashcard 16: Question: What is the role of phosphatidylserine in brain health? Answer: It supports neuronal membrane function and improves cognition, mood, and stress response. Flashcard 17: Question: Which neurotransmitter is most commonly associated with anxiety? Answer: GABA deficiency is linked with anxiety. Flashcard 18: Question: What type of diet has been shown to reduce symptoms of depression? Answer: The Mediterranean-style diet, rich in polyphenols and omega-3 fatty acids. Flashcard 19: Question: What supplement can be used to regulate the sleep-wake cycle in individuals with insomnia? Answer: Melatonin or 5-HTP. Flashcard 20: Question: Which neurotransmitter is critical for sleep regulation and is converted into melatonin? Answer: Serotonin. Flashcard 21: Question: What common food intolerances may trigger migraines? Answer: Gluten, dairy, and high-histamine foods like wine, cheese, and chocolate. Flashcard 22: Question: What nutrient deficiency is commonly linked to migraine sufferers? Answer: Magnesium deficiency. Flashcard 23: Question: Which mushroom is known for its neuroprotective effects and ability to support cognitive function? Answer: Lion's Mane (Hericium erinaceus). Flashcard 24: Question: Which amino acid is a precursor to both serotonin and melatonin? Answer: Tryptophan. Flashcard 25: Question: What role does the vagus nerve play in the gut-brain axis? Answer: It provides bidirectional communication between the gut and the brain, influencing mood and gut health. Flashcard 26: Question: What nutrient helps prevent oxidative stress and supports brain health? Answer: Vitamin C. Flashcard 27: Question: What herb can be used to reduce symptoms of anxiety by promoting GABA activity? Answer: Passionflower (Passiflora incarnata). Flashcard 28: Question: What dietary intervention can support neurotransmitter synthesis? Answer: A diet rich in protein, omega-3 fatty acids, and co-factors like B vitamins and magnesium. Flashcard 29: Question: What is the "tryptophan steal" and how does it affect serotonin levels? Answer: It occurs when tryptophan is diverted to produce NAD+ and ATP, reducing serotonin production, often due to stress or inflammation. Flashcard 30: Question: What supplement can help reduce cortisol levels and improve mood in individuals under stress? Answer: Phosphatidylserine, 100 mg taken 3 times a day.