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P2X7 receptor inhibition ameliorates dendritic spine pathology and social behavioral deficits in Rett syndrome mice

Author

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  • Juan Mauricio Garré

    (Columbia University Medical Center
    New York University School of Medicine)

  • Hernandez Moura Silva

    (New York University School of Medicine)

  • Juan J. Lafaille

    (New York University School of Medicine
    New York University School of Medicine)

  • Guang Yang

    (Columbia University Medical Center
    New York University School of Medicine)

Abstract

Dysregulated immunity has been implicated in the pathogenesis of neurodevelopmental disorders but its contribution to synaptic and behavioral deficits in Rett syndrome (RTT) remains unknown. P2X7 receptors (P2X7Rs) are unique purinergic receptors with pro-inflammatory functions. Here, we report in a MECP2-deficient mouse model of RTT that the border of the cerebral cortex exhibits increased number of inflammatory myeloid cells expressing cell-surface P2X7Rs. Total knockout of P2X7Rs in MECP2 deficient mice decreases the number of inflammatory myeloid cells, restores cortical dendritic spine dynamics, and improves the animals’ neurological function and social behavior. Furthermore, either genetic depletion of P2X7Rs in bone-marrow derived leukocytes or pharmacological block of P2X7Rs primarily outside of the central nervous system parenchyma, recapitulates the beneficial effects of total P2X7R depletion on the social behavior. Together, our results highlight the pathophysiological roles of P2X7Rs in a mouse model of RTT.

Suggested Citation

  • Juan Mauricio Garré & Hernandez Moura Silva & Juan J. Lafaille & Guang Yang, 2020. "P2X7 receptor inhibition ameliorates dendritic spine pathology and social behavioral deficits in Rett syndrome mice," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15590-5
    DOI: 10.1038/s41467-020-15590-5
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    Cited by:

    1. Pan Xu & Yuanlei Yue & Juntao Su & Xiaoqian Sun & Hongfei Du & Zhichao Liu & Rahul Simha & Jianhui Zhou & Chen Zeng & Hui Lu, 2022. "Pattern decorrelation in the mouse medial prefrontal cortex enables social preference and requires MeCP2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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