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Updated: Aug 15, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial Pten safeguards postnatal integrity of the cortex and sociability
Xing Zhou1,2,3, Jiacheng Wei1,2,3, Liang Li4
1Tsinghua-Peking Center for Life Sciences, Beijing, China.
Abstract:
Microglial abnormalities may contribute to neurodevelopmental disorders. PTEN is implicated as a susceptibility gene for autism spectrum disorders and its germline ablation in mice causes behavioral abnormalities. Here we find postnatal PTEN deletion in microglia causes deficits in sociability and novel object recognition test. Mutant mice harbor markedly more activated microglia that manifest enhanced phagocytosis. Interestingly, two-week postponement of microglia PTEN ablation leads to no social interaction defects, even though mutant microglia remain abnormal in adult animals. Disturbed neurodevelopment caused by early PTEN deletion in microglia is characterized by insufficient VGLUT1 protein in synaptosomes, likely a consequence of enhanced removal by microglia. In correlation, in vitro acute slice recordings demonstrate weakened synaptic inputs to layer 5 pyramidal neurons in the developing cortex. Therefore, microglial PTEN safeguards integrity of neural substrates underlying sociability in a developmentally determined manner.
Insights
Early deletion of PTEN in microglia impairs social behaviors in mice. This suggests microglial PTEN is crucial for proper neurodevelopment and social function during critical periods.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglial dysfunction is linked to neurodevelopmental disorders.
- PTEN gene mutations are associated with autism spectrum disorders (ASD).
Purpose of the Study:
- To investigate the role of PTEN in microglia during neurodevelopment.
- To determine the impact of postnatal microglial PTEN deletion on behavior and neural function.
Main Methods:
- Postnatal deletion of PTEN specifically in microglia of mice.
- Behavioral testing including sociability and novel object recognition.
- Analysis of microglial activation, phagocytosis, and synaptic integrity (VGLUT1 protein levels).
- In vitro acute slice electrophysiology.
Main Results:
- Postnatal microglial PTEN deletion caused deficits in social interaction and object recognition.
- Mutant microglia exhibited increased activation and phagocytosis.
- Delayed PTEN deletion prevented social deficits, despite persistent microglial abnormalities.
- Early deletion led to reduced VGLUT1 protein in synaptosomes and weakened synaptic inputs.
Conclusions:
- Microglial PTEN is essential for safeguarding neural substrates of sociability.
- Its function is critical during a specific developmental window.
- Microglial PTEN protects against excessive synaptic pruning during development.
