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Updated: Jun 18, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia-associated granule cell death in the normal adult dentate gyrus
Charles E Ribak1, Lee A Shapiro, Zachary D Perez
1Department of Anatomy and Neurobiology, School of Medicine, University of California at Irvine, Irvine, CA 92697-1275, USA. ribak@uci.edu
Abstract:
Microglial cells are constantly monitoring the central nervous system for sick or dying cells and pathogens. Previous studies showed that the microglial cells in the dentate gyrus have a heterogeneous morphology with multipolar cells in the hilus and fusiform cells apposed to the granule cell layer both at the hilar and at the molecular layer borders. Although previous studies showed that the microglia in the dentate gyrus were not activated, the data in the present study show dying granule cells apposed by Iba1-immunolabeled microglial cell bodies and their processes both at hilar and at molecular layer borders of the granule cell layer. Initially, these Iba1-labeled microglial cells surround individual, intact granule cell bodies. When small openings in the plasma membrane of granule cells are observed, microglial cells are apposed to these openings. When larger openings in the plasma membrane occur at this site of apposition, the granule cells display watery perikaryal cytoplasm, watery nucleoplasm and damaged organelles. Such morphological features are characteristic of neuronal edema. The data also show that following this localized disintegration of the granule cell's plasma membrane, the Iba1-labeled microglial cell body is found within the electron-lucent perikaryal cytoplasm of the granule cell, where it is adjacent to the granule cell's nucleus which is deformed. We propose that granule cells are dying by a novel microglia-associated mechanism that involves lysis of their plasma membranes followed by neuronal edema and nuclear phagocytosis. Based on the morphological evidence, this type of cell death differs from either apoptosis or necrosis.
Insights
Microglia in the dentate gyrus engage dying granule cells through a novel mechanism. This process involves plasma membrane lysis, neuronal edema, and nuclear phagocytosis, distinct from apoptosis or necrosis.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Microglial cells survey the central nervous system for cellular damage and pathogens.
- Previous research indicated heterogeneous microglial morphology in the dentate gyrus without signs of activation.
Purpose of the Study:
- To investigate the interaction between microglial cells and dying granule cells in the dentate gyrus.
- To characterize the morphological features of microglia-associated granule cell death.
Main Methods:
- Utilized Iba1-immunolabeling to identify microglial cells.
- Employed electron microscopy to examine the ultrastructural changes during granule cell death.
- Morphological analysis of microglial-granule cell interactions at different stages of cell death.
Main Results:
- Observed Iba1-labeled microglia interacting with dying granule cells at the hilar and molecular layer borders.
- Documented microglial cells surrounding intact granule cells, apposing small plasma membrane openings, and engulfing damaged cellular contents.
- Identified morphological characteristics of neuronal edema and nuclear deformation within dying granule cells.
Conclusions:
- Proposed a novel microglia-associated mechanism for granule cell death involving plasma membrane lysis, neuronal edema, and nuclear phagocytosis.
- This observed cell death pathway appears distinct from classical apoptosis or necrosis.
- Microglial cells play a critical role in clearing dying neurons via a unique phagocytic process.
