Microglial Prrc2a regulates microglia-neuron interaction in cerebellum and motor functions in mice
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 <i>Prrc2a</i>-ablated microglia, revealing an abnormally activated state. <i>Prrc2a</i> 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.
Authors
- Rui Wu (ORCID: https://orcid.org/0000-0001-7910-6614)
- Lingling Jiang (ORCID: https://orcid.org/0000-0003-4694-6419)
- Run-Ze Gu
- Ningsheng Shao
- Shuoshuo Li (ORCID: https://orcid.org/0000-0003-3499-2717)
- Jia Guo (ORCID: https://orcid.org/0000-0003-3216-8628)
- Jinbo Cheng (ORCID: https://orcid.org/0000-0002-3627-8544)
- Ruijuan Xiu (ORCID: https://orcid.org/0000-0002-1446-2711)
- Ying Shen (ORCID: https://orcid.org/0000-0002-3220-904X)
- Zengqiang Yuan (ORCID: https://orcid.org/0000-0001-5739-2867)
- Ping Zhang (ORCID: https://orcid.org/0000-0002-2295-9170)
- Jinyu Zhang (ORCID: https://orcid.org/0000-0002-0628-8856)
- Fengchao Wang (ORCID: https://orcid.org/0000-0002-4499-8103)
- Pin Yang
- Xiaoheng Li (ORCID: https://orcid.org/0000-0003-2943-119X)
- Binbin Dong
- Ao Li (ORCID: https://orcid.org/0009-0009-7888-0478)
Institutions
- Hebei Medical University (CN)
- Minzu University of China (CN)
- Beijing University of Chinese Medicine (CN)
- Anhui Medical University (CN)
- Sir Run Run Shaw Hospital (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Chinese Institute for Brain Research (CN)
- University of Chinese Academy of Sciences (CN)
- Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
- Southern Medical University (CN)
- University of South China (CN)
Publication Details
- Journal
- iScience
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1016/j.isci.2025.113949
- Citations
- 1
- Primary Topic
- Nuclear Receptors and Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.91