TY  - JOUR
AU  - Bahari-Javan, Sanaz
AU  - Maddalena, Andrea
AU  - Kerimoglu, Cemil
AU  - Wittnam, Jessica
AU  - Held, Torsten
AU  - Bähr, Mathias
AU  - Burkhardt, Susanne
AU  - Delalle, Ivanna
AU  - Kügler, Sebastian
AU  - Fischer, Andre
AU  - Sananbenesi, Farahnaz
TI  - HDAC1 regulates fear extinction in mice.
JO  - The journal of neuroscience
VL  - 32
IS  - 15
SN  - 0270-6474
CY  - Washington, DC
PB  - Soc.57413
M1  - DZNE-2020-02803
SP  - 5062-5073
PY  - 2012
AB  - Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, little is known about the role of individual HDAC proteins during the pathogenesis of brain diseases. HDAC1 was found to be upregulated in patients suffering from neuropsychiatric diseases. Here, we show that virus-mediated overexpression of neuronal HDAC1 in the adult mouse hippocampus specifically affects the extinction of contextual fear memories, while other cognitive abilities were unaffected. In subsequent experiments we show that under physiological conditions, hippocampal HDAC1 is required for extinction learning via a mechanism that involves H3K9 deacetylation and subsequent trimethylation of target genes. In conclusion, our data show that hippocampal HDAC1 has a specific role in memory function.
KW  - Acoustic Stimulation
KW  - Animals
KW  - Benzamides: administration & dosage
KW  - Benzamides: pharmacology
KW  - Blotting, Western
KW  - Chromatin Immunoprecipitation
KW  - Electroshock
KW  - Exploratory Behavior: physiology
KW  - Extinction, Psychological: physiology
KW  - Fear: physiology
KW  - Hippocampus: cytology
KW  - Hippocampus: drug effects
KW  - Histone Deacetylase 1: antagonists & inhibitors
KW  - Histone Deacetylase 1: genetics
KW  - Histone Deacetylase 1: physiology
KW  - Histone Deacetylase Inhibitors: administration & dosage
KW  - Histone Deacetylase Inhibitors: pharmacology
KW  - Immunohistochemistry
KW  - Male
KW  - Maze Learning: physiology
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Microinjections
KW  - Neurons: metabolism
KW  - Postural Balance: physiology
KW  - Pyridines: administration & dosage
KW  - Pyridines: pharmacology
KW  - Real-Time Polymerase Chain Reaction
KW  - Recognition, Psychology: physiology
KW  - Reflex, Startle: physiology
KW  - Swimming: psychology
KW  - Benzamides (NLM Chemicals)
KW  - Histone Deacetylase Inhibitors (NLM Chemicals)
KW  - Pyridines (NLM Chemicals)
KW  - entinostat (NLM Chemicals)
KW  - Hdac1 protein, mouse (NLM Chemicals)
KW  - Histone Deacetylase 1 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:22496552
C2  - pmc:PMC6622110
DO  - DOI:10.1523/JNEUROSCI.0079-12.2012
UR  - https://pub.dzne.de/record/136481
ER  -