Frontiers in Immunology (Dec 2022)
Microglial Pten safeguards postnatal integrity of the cortex and sociability
- Xing Zhou,
- Xing Zhou,
- Xing Zhou,
- Jiacheng Wei,
- Jiacheng Wei,
- Jiacheng Wei,
- Liang Li,
- Zhenfeng Shu,
- Ling You,
- Ling You,
- Yang Liu,
- Yang Liu,
- Ruozhu Zhao,
- Ruozhu Zhao,
- Ruozhu Zhao,
- Jiacheng Yao,
- Jiacheng Yao,
- Jianbin Wang,
- Jianbin Wang,
- Minmin Luo,
- Minmin Luo,
- Yousheng Shu,
- Kexin Yuan,
- Kexin Yuan,
- Hai Qi,
- Hai Qi,
- Hai Qi,
- Hai Qi,
- Hai Qi
Affiliations
- Xing Zhou
- Tsinghua-Peking Center for Life Sciences, Beijing, China
- Xing Zhou
- Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China
- Xing Zhou
- Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- Jiacheng Wei
- Tsinghua-Peking Center for Life Sciences, Beijing, China
- Jiacheng Wei
- Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China
- Jiacheng Wei
- Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- Liang Li
- Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
- Zhenfeng Shu
- Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
- Ling You
- Department of Bioengineering, School of Medicine, Tsinghua University, Beijing, China
- Ling You
- IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China
- Yang Liu
- School of Life Sciences, Tsinghua University, Beijing, China
- Yang Liu
- National Institute of Biological Science, Beijing, China
- Ruozhu Zhao
- Tsinghua-Peking Center for Life Sciences, Beijing, China
- Ruozhu Zhao
- Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China
- Ruozhu Zhao
- Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- Jiacheng Yao
- Tsinghua-Peking Center for Life Sciences, Beijing, China
- Jiacheng Yao
- School of Life Sciences, Tsinghua University, Beijing, China
- Jianbin Wang
- Tsinghua-Peking Center for Life Sciences, Beijing, China
- Jianbin Wang
- School of Life Sciences, Tsinghua University, Beijing, China
- Minmin Luo
- School of Life Sciences, Tsinghua University, Beijing, China
- Minmin Luo
- National Institute of Biological Science, Beijing, China
- Yousheng Shu
- Department of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China
- Kexin Yuan
- Department of Bioengineering, School of Medicine, Tsinghua University, Beijing, China
- Kexin Yuan
- IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China
- Hai Qi
- Tsinghua-Peking Center for Life Sciences, Beijing, China
- Hai Qi
- Laboratory of Dynamic Immunobiology, Institute for Immunology, Tsinghua University, Beijing, China
- Hai Qi
- Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China
- Hai Qi
- Beijing Key Laboratory for Immunological Research on Chronic Diseases, Tsinghua University, Beijing, China
- Hai Qi
- 0Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China
- DOI
- https://doi.org/10.3389/fimmu.2022.1059364
- Journal volume & issue
-
Vol. 13
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.
Keywords
