Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis

Leschik, Julia and Gentile, Antonietta and Cicek, Cigdem and Peron, Sophie and Tevosian, Margaryta and Beer, Annika and Radyushkin, Konstantin and Bludau, Anna and Ebner, Karl and Neumann, Inga and Singewald, Nicolas and Berninger, Benedikt and Lessmann, Volkmar and Lutz, Beat (2022) Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis. PROGRESS IN NEUROBIOLOGY, 217: 102333. ISSN 0301-0082, 1873-5118

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Abstract

The neurotrophin brain-derived neurotrophic factor (BDNF) stimulates adult neumgenesis, but also influences structural plasticity and function of semtonergic neurons. Both, BDNF/TrkB signaling and the serotonergic system modulate behavioral responses to stress and can lead to pathological states when dysregulated. The two systems have been shown to mediate the therapeutic effect of antidepressant drugs and to regulate hippocampal neurogenesis. To elucidate the interplay of both systems at cellular and behavioral levels, we generated a transgenic mouse line that overexpresses BDNF in serotonergic neurons in an inducible manner. Besides displaying enhanced hippocampus-dependent contextual learning, transgenic mice were less affected by chronic social defeat stress (CSDS) compared to wild-type animals. In parallel, we observed enhanced serotonergic axonal sprouting in the dentate gyrus and increased neural stem/progenitor cell proliferation, which was uniformly distributed along the dorsoventral axis of the hippocampus. In the forced swim test, BDNF-overexpressing mice behaved similarly as wild-type mice treated with the antidepressant fluoxetine. Our data suggest that BDNF released from serotonergic projections exerts this effect partly by enhancing adult neurogenesis. Furthermore, independently of the genotype, enhanced neumgenesis positively correlated with the social interaction time after the CSDS, a measure for stress resilience.

Item Type: Article
Uncontrolled Keywords: SYNAPTIC PLASTICITY; SOCIAL DEFEAT; RAPHE NUCLEUS; BDNF; DEPRESSION; RECEPTOR; CELLS; MODEL; AXONS; SUSCEPTIBILITY; BDNF; Serotonin; Adult neurogenesis; Stress; Resilience
Subjects: 500 Science > 590 Zoological sciences
Divisions: Biology, Preclinical Medicine > Institut für Zoologie > Tierphysiologie/Neurobiologie (Prof. Dr. Inga Neumann)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 29 Jan 2024 14:54
Last Modified: 29 Jan 2024 14:54
URI: https://pred.uni-regensburg.de/id/eprint/58629

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