RT Journal Article
T1 Neuronal Activity, TGFβ-Signaling and Unpredictable Chronic Stress Modulate Transcription of Gadd45 Family Members and DNA Methylation in the Hippocampus
A1 Grassi, Daniela
A1 Franz, Henriette
A1 Vezzali, Riccardo
A1 Bovio, Patrick
A1 Heidrich, Stefanie
A1 Dehghanian, Fariba
A1 Belzung, Catherine
A1 Krieglstein, Kerstin
A1 Vogel, Tanja
A1 Lagunas García, Luisa Natalia
AB Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members are associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice. UCMS led to reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.
PB Oxford University Press
SN 1047-3211
SN 1460-2199
YR 2017
FD 2017-04-21
LK https://hdl.handle.net/20.500.14352/95211
UL https://hdl.handle.net/20.500.14352/95211
LA eng
DS Docta Complutense
RD 12 abr 2025