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Updated: Aug 7, 2025
Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
Single-cell RNA sequencing identifies hippocampal microglial dysregulation in diet-induced obesity
Rosemary E Henn1,2, Kai Guo1,2, Sarah E Elzinga1,2
1Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
Abstract:
Obesity is a growing global concern in adults and youth with a parallel rise in associated complications, including cognitive impairment. Obesity induces brain inflammation and activates microglia, which contribute to cognitive impairment by aberrantly phagocytosing synaptic spines. Local and systemic signals, such as inflammatory cytokines and metabolites likely participate in obesity-induced microglial activation. However, the precise mechanisms mediating microglial activation during obesity remain incompletely understood. Herein, we leveraged our mouse model of high-fat diet (HFD)-induced obesity, which mirrors human obesity, and develops hippocampal-dependent cognitive impairment. We assessed hippocampal microglial activation by morphological and single-cell transcriptomic analysis to evaluate this heterogeneous, functionally diverse, and dynamic class of cells over time after 1 and 3 months of HFD. HFD altered cell-to-cell communication, particularly immune modulation and cellular adhesion signaling, and induced a differential gene expression signature of protein processing in the endoplasmic reticulum in a time-dependent manner.
Insights
Obesity impairs cognitive function by activating brain microglia, which damage synaptic spines. High-fat diets in mice reveal time-dependent changes in microglial immune signaling and protein processing, impacting brain health.
Area of Science:
- Neuroscience
- Immunology
- Metabolic Disorders
Background:
- Obesity is a global health issue linked to cognitive impairment.
- Obesity-induced brain inflammation and microglial activation contribute to cognitive decline.
- Mechanisms of microglial activation in obesity are not fully understood.
Purpose of the Study:
- To investigate the impact of high-fat diet (HFD)-induced obesity on hippocampal microglial activation and cognitive function in a mouse model.
- To analyze time-dependent changes in microglial characteristics and gene expression following HFD.
Main Methods:
- Utilized a mouse model of HFD-induced obesity.
- Assessed cognitive impairment and hippocampal microglial activation.
- Employed morphological and single-cell transcriptomic analysis at 1 and 3 months post-HFD.
Main Results:
- HFD induced cognitive impairment and altered hippocampal microglial morphology.
- Single-cell transcriptomics revealed time-dependent changes in microglial populations.
- HFD impacted cell-to-cell communication, immune modulation, cellular adhesion, and endoplasmic reticulum protein processing.
Conclusions:
- HFD-induced obesity triggers specific microglial responses in the hippocampus.
- These changes in microglial function and communication are time-dependent.
- Understanding these mechanisms is crucial for addressing obesity-related cognitive impairment.
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