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Papers of the Week

Papers: 9 Dec 2023 - 15 Dec 2023

2023 Dec 04

Int J Mol Sci




Transient Receptor Potential Vanilloid 4-Dependent Microglial Function in Myelin Injury and Repair.


Holloman JP, Dimas SH, Archambault AS, Filipello F, Du L, Feng J, Zhao Y, Bollman B, Piccio L, Steelman AJ, Hu H, Wu GF


Microglia are found pathologically at all stages of multiple sclerosis (MS) lesion development and are hypothesized to contribute to both inflammatory injury and neuroprotection in the MS brain. Transient receptor potential vanilloid 4 (TRPV4) channels are widely expressed, play an important role as environmental sensors, and are involved in calcium homeostasis for a variety of cells. TRPV4 modulates myeloid cell phagocytosis in the periphery and microglial motility in the central nervous system. We hypothesized that TRPV4 deletion would alter microglia phagocytosis in vitro and lessen disease activity and demyelination in experimental autoimmune encephalitis (EAE) and cuprizone-induced demyelination. We found that genetic deletion of TRPV4 led to increased microglial phagocytosis in vitro but did not alter the degree of demyelination or remyelination in the cuprizone mouse model of MS. We also found no difference in disease in EAE following global or microglia-specific deletion of . Additionally, lesioned and normal appearing white matter from MS brains exhibited similar expression compared to healthy brain tissue. Taken together, these findings indicate that TRPV4 modulates microglial activity but does not impact disease activity in mouse models of MS, suggesting a muted and/or redundant role in MS pathogenesis.