Cellular and Molecular Neurobiology
Author: Benjamín Isaías de la Cruz-Thea | email: bdlcruzthea@immf.uncor.edu
Benjamín I. de la Cruz-Thea 1°, María F. Harman 1°, Mauricio G. Martín 1°
1° Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra (INIMEC-CONICET-UNC), Universidad Nacional de Córdoba, Córdoba, Argentina.
Aging is associated to epigenetic alterations which lead to diminished expression of memory-related genes. One of the most important changes is the decrease in histone acetylation produced by the Histone Deacetylase 2 (HDAC2) activity. This process has been described as determinant for memory loss during aging. In this work we demonstrate that aging triggers the accumulation of HDAC2 in regulatory regions of the BDNF gene, a key transcription factor for synaptic plasticity. We found that the transcriptional co-repressor Chromodomain Y like protein (CDYL), which interacts with HDAC2 in hippocampal extracts, is accumulated in the nucleus of old neurons. The co-accumulation of CDYL and HDAC2 was also observed in slices of old transgenic Thy-1(GFP) mice brain. Considering that CDYL degradation is triggered by synaptic activity, our data suggest that CDYL accumulation can be due to impaired NMDA receptor activity as a consequence of cholesterol depletion in old neurons. Moreover, we found that CDYL silencing in primary culture of cortical neurons induces a decrease in the levels of HDAC2 when compared to controls, highlighting the fact that CDYL accumulation could both recruit HDAC2 to BDNF promoter and regulate HDAC2 expression or stability through a still undescribed mechanism. The findings herein contribute to the understanding of the epigenetic processes underlying synaptic impairment during aging.