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Cited by 7Neuroinflammation and Neurodegeneration MechanismsGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

Microglial Pten safeguards postnatal integrity of the cortex and sociability

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Zhou, Xing, Wei, Jiacheng, Li, Liang, Shu, Zhenfeng, You, Ling, Liu, Yang, Zhao, Ruozhu, Yao, Jiacheng +5 more·2022·Frontiers in Immunology
DOI 10.3389/fimmu.2022.1059364PMC PMC9795847
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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.

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Crossref · 10.3389/fimmu.2022.1059364

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  • This cell specific response may be due to the activation of the PTEN pathway in glia as dysregulated PTEN protein in microglia leads to its abnormal activation.

    “This cell specific response may be due to the activation of the PTEN pathway in glia as dysregulated PTEN protein in microglia leads to its abnormal activation. 61”

    From Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations (2026) · cites this paper as [61]

    The Results section, “Postnatal Pten ablation leads to accumulation of activated microglia,” reports that PTEN ablation leads to an activated microglial state. This supports the claim about dysregulated PTEN and microglial activation, but the paper studies PTEN loss rather than showing that activation of a PTEN pathway in glia explains the citing document’s cell-specific response. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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References 70 · Cited by 7

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Authors
Zhou, X., Wei, J., Li, L., Shu, Z., You, L., Liu, Y., Zhao, R., Yao, J., Wang, J., Luo, M., Shu, Y., Yuan, K., & Qi, H.
Affiliations
  • Center for Life Sciences (CN)
  • Shanghai Medical College of Fudan University (CN)
  • Tsinghua University (CN)
  • National Institute of Biological Sciences, Beijing (CN)
Corresponding author
  • Yuan, Kexin
  • Qi, Hai
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2022-12-14
Volume
13
Pages
1059364-1059364
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2022.1059364
PMC
PMC9795847
OpenAlex
W4311417698
Cited by
7
References
70
Citations by year
2026: 3 · 2025: 2 · 2024: 1 · 2023: 1
FWCI
0.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Beijing Municipal Science and Technology Commission
  • Howard Hughes Medical Institute
  • National Natural Science Foundation of China
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
PTEN, microglia, sociability, autism spectrum disorder, brain development, postnatal development, microglial phagocytosis, microglial activation, VGLUT1, synaptosomes, synaptic input, novel object recognition
MeSH terms
Autism Spectrum Disorder, Animals, Cerebral Cortex, Neurons, Microglia, Pyramidal Cells, Mice

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