Targeting histone deacetylation for recovery of maternal deprivation-induced changes in BDNF and AKAP150 expression in the VTA.

Targeting histone deacetylation for recovery of maternal deprivation-induced changes in BDNF and AKAP150 expression in the VTA.
Exp Neurol. 2018 Aug 10;:
Authors: Shepard RD, Gouty S, Kassis H, Berenji A, Zhu W, Cox BM, Nugent FS
Abstract
Severe early life stressors increase the probability of developing psychiatric disorders later in life through modifications in neuronal circuits controlling brain monoaminergic signaling. Our previous work demonstrated that 24 h maternal deprivation (MD) in male Sprague Dawley rats modifies dopamine (DA) signaling from the ventral tegmental area (VTA) through changes at GABAergic synapses that were reversible by in vitro histone deacetylase (HDAC) inhibition which led to restoration of the scaffold A-kinase anchoring protein (AKAP150) signaling and subsequently recovered GABAergic plasticity (Authement et al., 2015). Using a combination of in situ hybridization, Western blots and immunohistochemistry, we confirmed that MD-induced epigenetic modifications at the level of histone acetylation were associated with an upregulation of HDAC2. MD also increased Akap5 mRNA levels in the VTA. Western blot analysis of AKAP150 protein expression showed an increase in synaptic levels of AKAP150 protein in the VTA with an accompanying decrease in synaptic levels of protein kinase A (PKA). Moreover, the abundance of mature brain-derived neurotrophic factor (BDNF) protein of VTA tissues from MD rats was signific...

Source: Experimental Neurology - August 10, 2018 Category: Neurology Authors: Shepard RD, Gouty S, Kassis H, Berenji A, Zhu W, Cox BM, Nugent FS Tags: Exp Neurol Source Type: research