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Related Experiment Video

Updated: Jan 6, 2026

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
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Age-Associated Transcriptomic and Epigenetic Alterations in Mouse Hippocampus.

Merve Bilgic1,2, Rinka Obata1,3, Vlada-Iuliana Panfil1,4

  • 1Laboratory of Molecular Neurobiology, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.

Aging Cell
|September 28, 2025
PubMed
Summary

Aging impacts brain cell function, particularly in the hippocampus. This study reveals cell-specific gene and chromatin changes, identifying BACH2 as a key regulator in aging neurons and glial cells.

Keywords:
BACH2agingchromatin accessibilitygliahippocampusneuronsingle‐nucleus multiometranscriptome

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Area of Science:

  • Neuroscience
  • Genomics
  • Aging Research

Background:

  • Aging is a risk factor for neurodegenerative diseases like Alzheimer's.
  • Cellular and molecular changes in aging brains are not fully understood, especially chromatin regulation.
  • The link between molecular alterations and age-related functional decline in specific cell types is unclear.

Purpose of the Study:

  • To systematically characterize cell type-specific gene regulatory networks in the aging mouse hippocampus.
  • To investigate the role of chromatin accessibility and gene expression in aging neurons and glial cells.
  • To identify potential regulators of aging-associated functional decline.

Main Methods:

  • Single-nucleus multiome (RNA and ATAC) sequencing of the mouse hippocampus.
  • Analysis of gene expression and chromatin accessibility across diverse cell types.
  • Identification of cell type-specific molecular changes during aging.

Main Results:

  • Reconstructed hippocampal cell type diversity, revealing distinct aging-related transcriptomic and chromatin changes.
  • Oligodendrocytes and dentate gyrus (DG) neurons showed the most significant alterations.
  • Aging-dependent chromatin changes were prominent in neurons, particularly affecting synaptic plasticity genes.
  • BACH2 was identified as a potential regulator of synaptic plasticity, cell death, and inflammation in aging DG neurons.

Conclusions:

  • Single-nucleus multiome analysis provides insights into cell type-specific aging mechanisms in the brain.
  • Chromatin regulation plays a significant role in neuronal aging and vulnerability to neurodegeneration.
  • BACH2 emerges as a key candidate regulator in the aging of DG neurons and associated functions.