TY - JOUR
T1 - Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis
AU - Leschik, Julia
AU - Gentile, Antonietta
AU - Cicek, Cigdem
AU - Peron, Sophie
AU - Tevosian, Margaryta
AU - Beer, Annika
AU - Radyushkin, Konstantin
AU - Bludau, Anna
AU - Ebner, Karl
AU - Neumann, Inga
AU - Singewald, Nicolas
AU - Berninger, Benedikt
AU - Lessmann, Volkmar
AU - Lutz, Beat
N1 - Funding Information:
We acknowledge Miklós Zöldi, Kata Kenesei, and István Katona for help with preliminary experiments. We would like to thank Danuta Dormann, Andrea Conrad, Ruth Jelinek, and Rodrigue Maloumby, for excellent technical support. Moreover, we thank Dusan Bartsch (ZI Mannheim) for providing the TPH2-CreERT2 mouse line. This work was funded by the German Research Foundation DFG (LE 1020/2–1 to V.L. and LU 775/5–1 to B.L., and CRC1193, subproject A02 to B.B. and B.L) and the Inneruniversitäre Forschungsförderung Stufe 1 of the University Medical Center of Mainz to S.P. Part of work was funded by the Austrian Science Fund (FWF I 3875 to N.S.) and byTUBITAK 2214-A scholarship to C.C. The authors report no biomedical financial interests or conflicts of interest.
Funding Information:
We acknowledge Miklós Zöldi, Kata Kenesei, and István Katona for help with preliminary experiments. We would like to thank Danuta Dormann, Andrea Conrad, Ruth Jelinek, and Rodrigue Maloumby, for excellent technical support. Moreover, we thank Dusan Bartsch (ZI Mannheim) for providing the TPH2-CreER T2 mouse line. This work was funded by the German Research Foundation DFG ( LE 1020/2–1 to V.L. and LU 775/5–1 to B.L. , and CRC1193 , subproject A02 to B.B. and B.L) and the Inneruniversitäre Forschungsförderung Stufe 1 of the University Medical Center of Mainz to S.P. Part of work was funded by the Austrian Science Fund (FWF I 3875 to N.S.) and by TUBITAK 2214-A scholarship to C.C.
Publisher Copyright:
© 2022 The Authors
PY - 2022/10
Y1 - 2022/10
N2 - The neurotrophin brain-derived neurotrophic factor (BDNF) stimulates adult neurogenesis, but also influences structural plasticity and function of serotonergic 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 neurogenesis positively correlated with the social interaction time after the CSDS, a measure for stress resilience.
AB - The neurotrophin brain-derived neurotrophic factor (BDNF) stimulates adult neurogenesis, but also influences structural plasticity and function of serotonergic 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 neurogenesis positively correlated with the social interaction time after the CSDS, a measure for stress resilience.
UR - http://www.scopus.com/inward/record.url?scp=85135097774&partnerID=8YFLogxK
U2 - 10.1016/j.pneurobio.2022.102333
DO - 10.1016/j.pneurobio.2022.102333
M3 - Article
SN - 0301-0082
VL - 217
JO - Progress in Neurobiology
JF - Progress in Neurobiology
M1 - 102333
ER -