2. Academic Validation
  3. Microglial Prrc2a regulates microglia-neuron interaction in cerebellum and motor functions in mice

Microglial Prrc2a regulates microglia-neuron interaction in cerebellum and motor functions in mice

  • iScience. 2025 Nov 5;28(12):113949. doi: 10.1016/j.isci.2025.113949.
Xiaoheng Li 1,  Pin Yang 1 2,  Binbin Dong 3,  Lingling Jiang 4,  Ruilian Xiu 5,  Jia Guo 6,  Shuoshuo Li 1 7,  Ping Zhang 8,  Runze Gu 9,  Ao Li 9,  Jinyu Zhang 1 10,  Rong Wu 1,  Fengchao Wang 11,  Ying Shen 3,  Ningsheng Shao 1,  Jinbo Cheng 1 9,  Zengqiang Yuan 1
Affiliations

Affiliations

  • 1 The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
  • 2 School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230022, China.
  • 3 Department of Physiology and Department of Neurology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 4 Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
  • 5 Department of Neurobiology, Hebei Medical University, Shijiazhuang 050017, China.
  • 6 Key Laboratory of Mass Spectrometry Imaging and Metabolomics, Minzu University of China, Beijing 100081, China.
  • 7 School of Life Science, Beijing University of Chinese Medicine, Beijing 100029, China.
  • 8 Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 9 Center on Translational Neuroscience, College of Life and Environmental Science, Minzu University of China, Beijing 100081, China.
  • 10 Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China.
  • 11 National Institute of Biological Sciences, Beijing 102206, China.
PMID: 41341849 DOI: 10.1016/j.isci.2025.113949
Abstract

The crosstalk between microglia and neuron has been recognized as a crucial process in the development and disorders of the central nervous system. The present study probes into the role of Prrc2a-a post-transcriptional regulator that binds and stabilizes transcripts pivotal for microglial development-specifically within cerebellar microglia using a microglia-targeted conditional knockout model, identifying it as a crucial regulator of microglial function. Single-cell RNA Sequencing underscored a transcriptomic shift in Prrc2a-ablated microglia, revealing an abnormally activated state. Prrc2a deficiency and the consequent alteration of cerebellar microglia were associated with reduced mutual interactions, altered Purkinje cell morphology and electrophysiological activity, decreased molecular layer width, and subsequently defects in motor balance and coordination. Collectively, this study provides insights into the molecular mechanisms underlying microglia-neuron interaction within the cerebellum.

Keywords

Cell biology; Molecular biology; Neuroscience.

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