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Related Experiment Video

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Transcriptomic profiling of microglia and astrocytes throughout aging.

Jie Pan1, Nana Ma1, Bo Yu2,3

  • 1Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, China.

Journal of Neuroinflammation
|April 3, 2020
PubMed
Summary

Microglia and astrocytes show age-related gene changes in aging and Alzheimer's disease (AD). Most age-up genes were elevated in AD mice, highlighting their role in AD pathology.

Keywords:
AgingAlzheimer’s disease (AD)AstrocyteMicrogliaRNA-seq

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Area of Science:

  • Neuroscience
  • Genomics
  • Immunology

Background:

  • Microglia and astrocyte activation is a hallmark of aging and Alzheimer's disease (AD).
  • The specific cellular and molecular mechanisms driving these changes remain largely unknown.
  • Understanding these mechanisms is crucial for developing effective AD therapies.

Purpose of the Study:

  • To investigate age-related gene expression profiles in microglia and astrocytes.
  • To compare gene expression between wild-type and AD mouse models.
  • To identify molecular pathways involved in aging and AD pathogenesis.

Main Methods:

  • RNA sequencing (RNA-seq) was performed on isolated microglia and astrocytes.
  • Samples were obtained from wild-type and APP-PS1 (AD) mouse brains.
  • Five distinct time points were analyzed to capture age-related changes.

Main Results:

  • A set of age-related genes ('age-up'/'age-down') showed consistent changes in microglia and astrocytes from 4 months onward.
  • Most 'age-up' genes were significantly upregulated in AD mice compared to wild-type mice.
  • Bioinformatic analysis linked microglial 'age-up' genes to inflammation and astrocyte 'age-up' genes to AD risk, synaptic function, and peptidase inhibition.

Conclusions:

  • RNA-seq data provide a comprehensive resource for studying glial cell roles in aging and AD.
  • Identified gene expression patterns offer insights into microglia and astrocyte contributions to AD pathology.
  • This study lays the groundwork for future research into therapeutic targets for AD.