Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression

Grassmé H, Jernigan PL, Hoehn RS, Wilker B, Soddemann M, Edwards MJ, Müller CP, Kornhuber J, Gulbins E (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Neurosignals Karger

Book Volume: 23

Pages Range: 84-92

Journal Issue: 1

DOI: 10.1159/000442606

Abstract

Major depressive disorder is a common disease with serious morbidity, including increased risk of death from suicide. Major depressive disorder is treated with antidepressants. However, the molecular targets of antidepressants remained ill-defined and require further elucidation.Mice were treated with corticosterone to induce stress, amitriptyline and the p38-kinase (p38K) inhibitor SB239063 or a combination of these drugs. Phosphorylation of p38K in hippocampal neurons was determined by immunostaining with a phospho-specific antibody, neuronal proliferation using BrdU-labelling and behaviour employing a set of behavioural tests.Corticosterone induced phosphorylation/activation of p38K in the hippocampus in vivo. Antidepressants reversed the effect of corticosterone on p38K activation in wildtype mice, but had no effect in acid sphingomyelinase-deficient animals. Corticosterone also reduced neurogenesis and triggered depression-like behavioural changes, effects that were prevented by pharmacological inhibition of p38K.Stress induces p38K phosphorylation/activation in the hippocampus and thereby reduces neurogenesis and induces depression-like symptoms, events that are prevented by antidepressants via inhibition of the acid sphingomyelinase/ceramide system.

Authors with CRIS profile

Peter Christian Müller Professur für Suchtmedizin Johannes Kornhuber Lehrstuhl für Psychiatrie und Psychotherapie

Involved external institutions

University of Cincinnati US United States (USA) (US) Universität Duisburg-Essen (UDE) DE Germany (DE)

How to cite

APA:

Grassmé, H., Jernigan, P.L., Hoehn, R.S., Wilker, B., Soddemann, M., Edwards, M.J.,... Gulbins, E. (2015). Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression. Neurosignals, 23(1), 84-92. https://doi.org/10.1159/000442606

MLA:

Grassmé, Heike, et al. "Inhibition of Acid Sphingomyelinase by Antidepressants Counteracts Stress-Induced Activation of P38-Kinase in Major Depression." Neurosignals 23.1 (2015): 84-92.

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