NCBP1 Improves Cognitive Function in Mice by Reducing Oxidative Stress, Neuronal Loss, and Glial Activation After Status Epilepticus.

Abstract

Status epilepticus (SE) is a severe manifestation of epilepsy which can cause neurologic injury and death. This study aimed to identify key proteins involved in the pathogenesis of epilepsy and find a potential drug target for SE treatment. Tandem mass tag (TMT)-based quantitative proteomic analysis was applied to screen differentially expressed proteins (DEPs) in epilepsy. The adeno-associated virus was employed to overexpress candidate DEP in mice, and kainic acid (KA) was used to generate a mouse model of epilepsy. Then histopathological examination of the hippocampal tissue was performed, and the inflammatory factors levels in serum and hippocampus were measured. The IP-MS analysis was carried out to identify the interacting protein of nuclear cap-binding protein 1 (NCBP1). The results were that NCBP1 was downregulated in the epileptic hippocampus. NCBP1 overexpression alleviated KA-induced cognitive impairment in mice and reduced the apoptosis and damage of hippocampal neurons. Additionally, overexpressed NCBP1 increased the expression of NeuN and reduced the expression of GFAP and IBA-1 in the hippocampus of the mice. Further study indicated that NCBP1 overexpression inhibited the expression of IL-6, IL-1β, and IFN-γ in serum and hippocampus as well as MDA and LDH in the hippocampus, whereas it increased the SOD levels, suggesting that overexpression of NCBP1 could diminish KA-induced inflammatory responses and oxidative stress. The IP-MS analysis identified that ELAVL4 was the NCBP1-interacting protein. In conclusion, this finding suggests that NCBP1 may potentially serve as a drug target for the treatment of epilepsy.