Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer’s disease
Yuan‐Ting Sun, Jinran Li, Nan A, Zhaoxing Li, Wenyi Zhong, Long Chen, Sai Liu, Bocheng Zhang, Zheying Zhu, Xinuo Li
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disease and linked to abnormal deposition of amyloid-β (Aβ), neurofibrillary tangles (NFTs), synaptic dysfunction, and neuroinflammation. Despite significant progress in unravelling the pathogenesis of AD, currently main therapeutic interventions is limited to symptomatic alleviation. Methylprednisolone (MP), a synthetic glucocorticoid, is recognized for its extensive anti-inflammatory properties. Our study assessed the neuroprotective effect of MP (25 mg/kg) administration to an Aβ 1-42 -induced AD mouse model. Our findings demonstrate that MP treatment can ameliorate cognitive impairment in Aβ 1-42 -induced AD mice and suppress microglial activation in the cortex and hippocampus. RNA-Sequencing analysis reveals that MP ultimately rescues cognitive dysfunction through improving the synapse function and inhibiting the immune and inflammatory processes. Our study suggests that MP could be a promising drug alternative for the treatment of AD, either alone or in combination with other existing drugs.