Abstract
Epithelial sodium channel (ENaC) is responsible for regulating Na+ homeostasis. While its physiological functions have been investigated extensively in peripheral tissues, far fewer studies have explored its functions in the brain. Since our limited knowledge of ENaC’s distribution in the brain impedes our understanding of its functions there, we decided to explore the whole-brain expression pattern of the Scnn1a gene, which encodes the core ENaC complex component ENaCα. To visualize Scnn1a expression in the brain, we crossed Scnn1a-Cre mice with Rosa26-lsl-tdTomato mice. Brain sections were subjected to immunofluorescence staining using antibodies against NeuN or Myelin Binding Protein (MBP), followed by the acquisition of confocal images. We observed robust tdTomato fluorescence not only in the soma of cortical layer 4, the thalamus, and a subset of amygdalar nuclei, but also in axonal projections in the hippocampus and striatum. We also observed expression in specific hypothalamic nuclei. Contrary to previous reports, however, we did not detect significant expression in the circumventricular organs, which are known for their role in regulating Na+ balance. Finally, we detected fluorescence in cells lining the ventricles and in the perivascular cells of the median eminence. Our comprehensive mapping of Scnn1a-expressing cells in the brain will provide a solid foundation for further investigations of the physiological roles ENaC plays within the central nervous system.
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Funding
This work was supported by National Research Foundation of Korea (NRF) grants funded by the Korean Government (the Ministry of Science and ICT, RS-2023-00208193, and NRF-2022M3A9F3094559 to Y.T.J.), by Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Health & Welfare, 21C0712L1 to Y.T.J.), and by Korea University grant (K2117151 to Y.T.J.)
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HKK and YTJ conceptualized and designed the research. HKK conducted the immunohistochemistry experiments and acquired confocal microscopic images. HKK, SHC, DHK, and YTJ analyzed and interpreted the data. YTJ reanalyzed single cell RNA sequencing data, supervised the project and wrote the paper. All authors read and approved the final manuscript.
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Kim, H.K., Choi, SH., Kim, DH. et al. Comprehensive mapping of Epithelial Na+ channel α expression in the mouse brain. Brain Struct Funct 229, 681–694 (2024). https://doi.org/10.1007/s00429-023-02755-3
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DOI: https://doi.org/10.1007/s00429-023-02755-3