Mikroglia als Vermittler immuno-logischer Aspekte der Depression

A. Friebe; S. Wachholz; M. Esslinger; M. Schäfer

doi:10.1055/s-0038-1627746

Nervenheilkunde, Table of Contents

Nervenheilkunde 2014; 33(11): 780-789
DOI: 10.1055/s-0038-1627746

Mikroglia

Schattauer GmbH

Mikroglia als Vermittler immuno-logischer Aspekte der Depression

Microglia mediate immunological aspects of depression

A. Friebe

¹Klinik für Psychiatrie, Psychotherapie und Präventivmedizin, LWL-Universitätsklinik der Ruhr-Universität Bochum

,

S. Wachholz

¹Klinik für Psychiatrie, Psychotherapie und Präventivmedizin, LWL-Universitätsklinik der Ruhr-Universität Bochum

,

M. Esslinger

¹Klinik für Psychiatrie, Psychotherapie und Präventivmedizin, LWL-Universitätsklinik der Ruhr-Universität Bochum

,

M. Schäfer

²Klinik für Psychiatrie, Psychotherapie, Psychosomatik und Suchtmedizin, Kliniken Essen-Mitte, Essen

› Author Affiliations

Abstract

Zusammenfassung

Eine Immunaktivierung geht häufig mit Verhaltensänderungen (sickness behavior) einher, die Teil der unspezifischen Immunantwort sind, über inflammatorische Zytokine gesteuert werden und durch veränderte Priorisierung von Aktivitäten zur erfolgreichen Immunabwehr beitragen. Bei chronischer Immunaktivität kann sich aus diesen Verhaltensänderungen ein depressives Syndrom entwickeln. Dieser Zusammenhang wurde anhand humaner Modelle (immunaktivierende Behandlung mit Interferon-alpha) bestätigt. Umgekehrt finden sich erhöhte Immunparameter auch bei primär depressiven Patienten und Studien zeigten antidepressive Effekte einer anti-inflammatorischen Add-on-Therapie. Psychischer Stress, der eine Aktivierung des peripheren Immunsystems bewirkt und Hauptrisikofaktor für die Entwicklung einer depressiven Episode ist, könnte hier als Bindeglied fungieren. Mikroglia sind an vorderster Front in inflammatorische Prozesse im ZNS involviert und parallel an der Aufrechterhaltung synaptischer Verbindungen beteiligt. Sie bilden eine wichtige Schnittstelle zwischen Inflammation und Neurotransmission. Sowohl inflammatorische Prozesse in der Peripherie als auch psychischer Stress führen zur Aktivierung von Mikroglia und triggern die Induktion eines pro-inflammatorischen, neurotoxischen Phänotyps. Freigesetzte Zytokine und neurotoxische Metabolite induzieren über vielfältige Mechanismen depressive Symptome und triggern degenerative Prozesse (Neuropilreduktion). Eine Beteiligung der Mikroglia in der Pathophysiologie der Depression wird vermutet.

Summary

An acute immune activation is accompanied by a change in behavior (sickness behavior), which is part of the innate immune response, develops under the control of inflammatory cytokines and contributes to a successful immune defense by changing prioritization of activities. In case of chronic immune activation, sickness behavior can turn into a depressive syndrome, which was confirmed in human models (immune activating therapy with Interferon alpha). Inflammatory parameters are also increased in primary depressed patients and clinical studies showed anti-depressive effects of an anti-inflammatory addon therapy. Psychological stress, which activates the peripheral immune system and is the main risk factor for a depressive episode, might serve as link for these observations. Microglia are involved as first line responders in inflammatory processes in the CNS and in the maintenance of synaptic connectivity. Thus, they serve as an important interface between inflammation and neurotransmission. Peripheral inflammation as well as psychological stress activates microglia and triggers a pro-inflammatory, neurotoxic phenotype. Released cytokines and neurotoxic metabolites induce depressive symptoms via diverse mechanisms and trigger degenerative processes (neuropil reduction). An involvement of microglia in the pathophysiology of depression is assumed.

Schlüsselwörter

Depression - Inflammation - Mikroglia - Zytokine

Keywords

Depression - inflammation - microglia - cytokines

Full Text

References

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