Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 87, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2020.106824
Keywords
TRPM2 ion channel; Epilepsy; Neuroinflammation; Neuronal degeneration; Autophagy; Cognitive impairment
Categories
Funding
- National Natural Science Foundation of China [81201511, 81671287, 81372116]
- Health Innovative Talents in Zhejiang Province
- Zhejiang Province Public Welfare Technology Application Research Project [LY15H090006, LQ19C090007]
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Neuroinflammation contributes to the generation of epileptic seizures and is associate with neuropathology and comorbidities. Transient receptor potential melastatin 2 (TRPM2) expresses in various cell types in the brain. It plays a pathological role in a wide range of neuroinflammatory diseases, but has yet been studied in epilepsy. Here, a temporal lobe epilepsy model was generated by pilocarpine administration in mice. M 24 h, knockout (KO) TRPM2 alleviated the level of neuroinflammation, showing a reduction of IL-1 beta, TNF-alpha, CXCL2 and IL-6 mRNA production, NLRP3, ASC, and Caspase-1 protein expression and glial activation. Moreover, KO TRPM2 alleviated neurodegeneration, concurrent with reduced Beclin-1 and ATG5 protein expression. Later, KO TRPM2 ameliorated the epilepsy-induced psychological disorders, with improved performance in the open-field, Y maze and novel object recognition test. Together, these results suggest that TRPM2 facilitates epilepsy-related brain injury and may shed light on its potential as a therapeutic target for epilepsy-associated neuropathology and comorbidities.
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