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A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
Published on: February 5, 2018
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Diminished LC3-Associated Phagocytosis by Huntington's Disease Striatal Astrocytes
Nicole M Wakida1, Alice L Lau2, Jessica Nguyen1
1Biomedical Engineering, Beckman Laser Institute, University of California, Irvine, Irvine, CA, USA.
Journal of Huntington'S Disease
|March 7, 2022
Summary
Phagocytosis, the engulfment of cellular debris by astrocytes, is impaired in Huntington's disease (HD) mouse models. This study reveals a progressive decline in this crucial astrocyte function as HD advances.
Area of Science:
- Neuroscience
- Cell Biology
- Neurodegeneration
Background:
- Astrocytes perform active roles in synapse modulation and cellular debris clearance.
- Astrocytes are implicated in both protective and pathogenic mechanisms influencing Huntington's disease (HD) progression.
Purpose of the Study:
- To investigate whether the phagocytosis of cellular debris is compromised in striatal astrocytes affected by Huntington's disease.
Main Methods:
- Primary adult astrocytes were isolated from R6/2 and Q175 mouse models of HD.
- Laser nanosurgery was used to lyse individual astrocytes within a network.
- Phagocytic responses were monitored using phase contrast and fluorescence microscopy (GFP-LC3).
Main Results:
- A significant reduction in astrocyte phagocytosis was observed in both HD mouse models, correlating with disease progression.
- The number of responding astrocytes and the average number of phagocytic vesicles per cell were diminished.
- LC3 (microtubule-associated protein 1A/1B-light chain 3) localization to phagocytic vesicles was impaired in HD astrocytes.
Conclusions:
- A progressive decrease in LC3-associated phagocytosis occurs in the striatal astrocytes of mice with Huntington's disease.
- This impaired phagocytosis may contribute to the pathogenesis of HD.
