Biochemie der Seele

Zusammenfassung

Toxischer Stress kann lebenslange Spuren im Gehirn hinterlassen, die das Risiko für Angst und Depressionen sowie für Herz-Kreislauf-Krankheiten erhöhen. Vor allem in kritischen Zeitfenstern während der prä- und neonatalen Entwicklung reagiert der Organismus sensibel auf Stress. Er führt zur anhaltenden Hyperaktivität der zentralen Stressachse, charakterisiert durch eine erhöhte Cortisol-Sekretion unter Ruhebedingungen und eine Überexpression des Stresshormons Vasopressin (AVP). DNA-Analysen zeigen eine starke Beteiligung epigenetischer Mechanismen. Im Vergleich zu Kontroll-Mäusen hatten gestresste Tiere ein dauerhaft verändertes Methylierungsmuster von Stressgenen in Gehirnregionen, die für die Stressregulation zuständig sind. Dabei verursacht die Demethylierung des AVP-Gens eine lebenslange Überproduktion dieses Hormons. Diese Überexpression ist zunächst reversibel (Soft-wiring), bevor sie mittels DNA-Methylierungen festgeschrieben wird (Hard-wiring). Daraus ergibt sich die Forderung, bei toxischem Stress frühzeitig therapeutisch einzugreifen, um den Übergang von Soft- in Hard-wiring zu verhindern.

Abstract

Toxic stress can leave lifelong traces in the brain, which increase the risk for anxiety and depression as well as cardiovascular disease. The human reacts sensitively to stress, especially within certain time windows during prenatal and neonatal development. This leads to sustained hyperactivity of the central stress axis, characterized by increased secretion of cortisol under resting conditions and overexpression of the stress hormone vasopressin (arginine vasopressin, AVP). DNA analyses have shown substantial involvement of epigenetic mechanisms. Compared with control mice, stressed mice had a permanently altered methylation pattern of stress genes in the cerebral regions that are responsible for stress regulations. Demethylation of the AVP gene triggers lifelong overproduction of the hormone. This overexpression is initially reversible (soft wiring) before it is encoded via DNA methylations (hard wiring). This means that in case of toxic stress, early therapeutic intervention is needed in order to prevent the transition from soft wiring into hard wiring.

Schlüsselwörter

früher Stress - Entwicklungsstörungen - HPA-Achse - Hyperaktivität - CpG-Methylierungen - Soft-Wiring - Hard-Wiring - Therapie

Keywords

early stress - developmental disorders - HPA axis - hyperactivity - CpG methylations - soft wiring - hard wiring - therapy

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