Chromatin Remodeling Factor SMARCA5 is Essential for Hippocampal Memory Maintenance via Metabolic Pathways in Mice

Neurosci Bull. 2023 Jul;39(7):1087-1104. doi: 10.1007/s12264-023-01032-x. Epub 2023 Feb 18.

Abstract

Gene transcription and new protein synthesis regulated by epigenetics play integral roles in the formation of new memories. However, as an important part of epigenetics, the function of chromatin remodeling in learning and memory has been less studied. Here, we showed that SMARCA5 (SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 5), a critical chromatin remodeler, was responsible for hippocampus-dependent memory maintenance and neurogenesis. Using proteomics analysis, we found protein expression changes in the hippocampal dentate gyrus (DG) after the knockdown of SMARCA5 during contextual fear conditioning (CFC) memory maintenance in mice. Moreover, SMARCA5 was revealed to participate in CFC memory maintenance via modulating the proteins of metabolic pathways such as nucleoside diphosphate kinase-3 (NME3) and aminoacylase 1 (ACY1). This work is the first to describe the role of SMARCA5 in memory maintenance and to demonstrate the involvement of metabolic pathways regulated by SMARCA5 in learning and memory.

Keywords: Chromatin remodeling; Epigenetic regulation; Hippocampal memory; Metabolic pathway; SMARCA5.

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly*
  • Hippocampus / metabolism
  • Memory*
  • Metabolic Networks and Pathways
  • Mice
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • Chromatin