Brain Online

5HTT

📝 Zuletzt geändert: (heute) 🆕📊 616 Wörter

5HTT

Status:
Tags: genetics science ai-generated

  • ist ein Serotonin-Transporter, welcher das Serotonin von der Synaspe wegtransportiert

aus Behave

5HTT codes for a transporter that removes serotonin from the synapse;
Seite 203 · Position 4065

🤖 AI addition (15/06/26):

The Serotonin System

Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine Neurotransmitter synthesized from the amino acid tryptophan:

Tryptophan → 5-HTP (tryptophan hydroxylase, rate-limiting) → Serotonin (aromatic L-amino acid decarboxylase)

The main source of serotonergic input to the brain is the dorsal raphe nucleus (DRN) in the brainstem, which projects diffusely to the cortex, limbic system, striatum, and spinal cord. The median raphe nucleus also contributes.


3D ball model of the serotonin molecule (5-hydroxytryptamine) showing the indole ring structure

Important: ~90% of the body’s serotonin is in the gut (enteric nervous system and enterochromaffin cells), where it regulates intestinal motility. Gut serotonin does not cross the blood-brain barrier — central and peripheral pools are separate.

5HTT / SERT: The Serotonin Transporter

5HTT (the gene) codes for SERT (serotonin transporter), also known as SLC6A4 (solute carrier family 6, member 4). SERT is a Na⁺/Cl⁻-dependent transporter located on the presynaptic membrane of serotonergic neurons.

Function: After serotonin is released into the synapse, SERT reuptakes it back into the presynaptic neuron → terminates the serotonin signal → serotonin is either repackaged into vesicles or broken down by MAO-A (monoamine oxidase A).

SSRIs block SERT: Selective serotonin reuptake inhibitors (fluoxetine, sertraline, escitalopram) bind SERT and prevent reuptake → more 5-HT remains in the synapse → prolonged and enhanced serotonergic signaling. This is the mechanism of the most widely prescribed antidepressants.

Serotonin’s Roles in the Brain

FunctionMechanism/Evidence
Mood regulationLow 5-HT associated with depression; SSRIs effective in ~50% of patients
AnxietyComplex: 5-HT1A activation → anxiolytic; 5-HT2A activation → anxiogenic
SleepDRN active during waking; 5-HT promotes wakefulness; precursor to melatonin
Appetite5-HT2C activation reduces food intake (target of weight-loss drugs)
Social behavior↑ 5-HT → ↑ prosocial, cooperative behavior; ↓ 5-HT → aggression and impulsivity
PainDescending serotonergic pathways modulate pain via dorsal horn
Cognition5-HT modulates memory consolidation and flexibility

5HTTLPR: The Short/Long Genetic Variant

One of the most studied gene-environment interactions in psychiatry:

5HTTLPR (5-HTT linked promoter region) is a functional polymorphism in the promoter of SLC6A4:

  • Long (l) allele: Higher SERT expression → more efficient serotonin reuptake
  • Short (s) allele: ~50% lower SERT expression → more 5-HT in synapse chronically, but paradoxically associated with greater vulnerability to depression and anxiety under stress

The interaction (Caspi et al., 2003 Science — heavily cited but also debated):

  • Individuals with ≥1 short allele who experience childhood maltreatment or adult life stressors are at higher risk for depression than those with two long alleles exposed to the same stressors
  • Pure main-effect of genotype (without stress) is weak or absent
  • This was a landmark gene × environment (GxE) interaction study — influenced by Sapolsky’s “Behave” and broader behavioral genetics

Note: Replication has been mixed; large meta-analyses are inconclusive. The original Caspi finding may require very specific stressor type (severe, early-life adversity). The effect is real but smaller and more context-dependent than initially reported.

Gut-Brain Serotonin Connection

  • Gut enterochromaffin cells sense luminal contents → release 5-HT → activates vagal afferents → signals to brainstem/brain
  • The gut microbiome influences serotonin synthesis: germ-free mice have ~60% lower colonic 5-HT; certain bacteria (e.g., spore-forming bacteria of Clostridia) upregulate 5-HT biosynthesis
  • SSRIs affect gut motility (common side effect: nausea, diarrhea early in treatment) via peripheral SERT blockade
  • Growing evidence that gut-derived signals via serotonin pathways influence mood — part of the gut-brain axis story (see Dopamin und Belohnung for parallel dopaminergic gut-brain signals)

See also

Superlink: Serotonin

Quellen

Chapter 8 Back to When You Were Just a Fertilized Egg
→ Einordnung: Neurotransmitter vs Neuropeptide vs Hormone · Neurotransmitter · Dopamin und Belohnung

Erstellt: 26-07-21 21:09