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Serotonin
Uni of Notts, Neurobiology of disease, second year, topic 4
| Term | Definition |
|---|---|
| How serotonin was discovered | Identified as a vasoconstrictor in blood vessel experiments & later chemically identified as 5-hydroxytryptamine (5-HT). Originally thought to be involved in hypotension (tonin) |
| Where in the body serotonin is produced (+general structure) | ~90% enterochromaffin cells in GI tract, ~8% platlets, ~2% CNS Indole ring with an amine |
| Where serotonin is produced in the CNS | In the raphe nuclei, projecting to forebrain, thalamus, cerebellum, & spinal cord |
| Serotonin synthesis | Tryptophan hydroxylated by tryptophan hydroxylase (rate-limiting step). 5-hydroxytryptophan decarboxylated by AADC to form serotonin |
| Logistical issues of CNS serotonin synthesis | Availability of tryptophan crossing the BBB |
| How tryptophan transport to CNS is affected | Albumin-bound tryptophan cannot cross the BBB, must dissociate first, & neutral amino acids compete with tryptophan for transport |
| How cortisol influences serotonin levels | High cortisol reduces free tryptophan & affects circadian rhythms, lowering serotonin synthesis contributing to depression causing a positive feedback loop |
| Melatonin | Derivative of serotonin; regulates circadian rhythms via MT1 & MT2 receptors everywhere in the brain but especially hypothalamus & hippocampus |
| Two main downstream signalling pathways of melatonin receptors | Gi-mediated inhibition of cAMP (↓PKA, reduced activity) & PLC activation (IP₃/DAG → ↑Ca²⁺, circadian regulation) |
| How melatonin synthesis is regulated by light | Light inhibits N-acetyltransferase, reducing melatonin production |
| Neuroprotective roles of melatonin | Acts as antioxidant, reduces oxidative stress, & may suppress amyloid aggregation & tau by regulating BACE1 transcription. Delays senescence by regulating PSEN1 gene for presenilin |
| Serotonin in the hypothalamus | Regulates neuroendocrine function & memory via hippocampal pathways. Implicated in memory disorders & migraines |
| Serotonin metabolism | MAO-A converts it to 5-HIAA via aldehyde intermediates, which is excreted |
| Difference between MAO-A and MAO-B | Both isoforms with ~7-% homology. MAO-A metabolises serotonin & noradrenaline; MAO-B mainly metabolises dopamine |
| How SERT functions | Reuptakes serotonin via Na⁺-dependent symport & K⁺ antiport |
| How SLC6A4 variation affects behaviour | Polymorphisms & repeats in SERT gene alter serotonin reuptake & are linked to anxiety traits |
| Serotonin receptor types | ~14 receptor subtypes across 7 families with diverse signalling mechanisms caused by alternative splicing |
| r5-HT1 | Decrease presynaptic neurotransmitter release usually as autoreceptors. Metabotropic Gi subunit activators. 5-HT1A is a target for mood. 5-HT1B is a target for migraines. 5-HTC similar to B. 5-HTE isn't understood |
| r5-HT2 | Excitatory Gq postsynaptic involved in perception. 5-HTA is the target for psychedelics. 5-HT2B is peripheral & controls heart valves. 5-HT2C postsynaptic controls appetite & mood, reduces DA |
| r5-HT3 | Ionotropic Na+/Ca++ rapid excitatory pre & post-synaptic in peripheral NS. Involved with nausea & vomiting, target for antiemetics |
| r5-HT4 | Excitatory Gs post-synaptic GI & CNS receptor. Promotes synaptic transmission rather than other downstream pathways |
| r5-HT5 | Inhibitory Gi post-synaptic. Poorly understood |
| r5-HT6 | Excitatory Gs postsynaptic. Involved in cognition & memory |
| r5-HT7 | Excitatory Gs postsynaptic. Circadian rhythm & mood |
| Serotonin receptors in astrocytes | They have all receptor families |
Created by:
Denny12
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