Cellular and Molecular Neurobiology
Author: Agostina Belén Rojas | Email: agostina.rojas@mi.unc.edu.ar
Agostina B. Rojas1°, Benjamín I. de la Cruz Thea1°,Mauricio G. Martín1°
1° Departamento de Neurobiología Celular y Molecular / Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET-UNC) / Universidad Nacional de Córdoba
Aging is associated with a decline in cognitive abilities, including alterations in episodic memory formation. Dysregulation of chromatin structure in response to synaptic activity is a major cause of these alterations.
Previous results from the laboratory have shown that neuronal cholesterol loss associated with aging affects NMDA and AMPA receptor activity and their downstream signalling pathway, altering the epigenetic regulation of genes such as BDNF, which are essential for memory formation.
Specifically, cholesterol loss induces the accumulation of repressor epigenetic marks such as HDAC2 in the BDNF gene, inhibiting its expression. Our data suggest that the transcriptional repression complex REST and the corepressor CDYL play a crucial role in this regulation. Indeed, our results show an accumulation of CDYL in old neurons and a reduced degradation of CDYL in response to a glutamate stimulus.
We propose that aging-associated neuronal cholesterol loss prevents CDYL degradation in aged neurons in vitro, reducing BDNF expression. We use in vitro cholesterol manipulation in hippocampal neurons to assess the relationship between cholesterol loss and CDYL accumulation in this cell type.