Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer's disease

Yuan Sun; Jinran Li; Nan A; Zhaoxing Li; Wenyi Zhong; Long Chen; Sai Liu; Bocheng Zhang; Zheying Zhu; Xinuo Li

doi:10.3389/fimmu.2023.1192940

Methylprednisolone alleviates cognitive functions through the regulation of neuroinflammation in Alzheimer's disease

Front Immunol. 2023 May 1:14:1192940. doi: 10.3389/fimmu.2023.1192940. eCollection 2023.

Authors

Yuan Sun¹, Jinran Li¹, Nan A², Zhaoxing Li³, Wenyi Zhong⁴, Long Chen¹, Sai Liu¹, Bocheng Zhang⁵, Zheying Zhu⁵, Xinuo Li¹

Affiliations

¹ Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
² Digestive Endoscopy Department, The First Affiliated Hospital with Nanjing Medical University and Jiangsu Province Hospital, Nanjing, China.
³ State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, China.
⁴ Department of Organic Chemistry, China Pharmaceutical University, Nanjing, China.
⁵ School of Pharmacy, The University of Nottingham, Nottingham, United Kingdom.

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.

Keywords: Alzheimer’s disease; cognitive function; methylprednisolone; microglial activation; neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / drug therapy
Alzheimer Disease* / pathology
Amyloid beta-Peptides / pharmacology
Animals
Cognition
Methylprednisolone / adverse effects
Mice
Neurodegenerative Diseases*
Neuroinflammatory Diseases

Substances

Methylprednisolone
Amyloid beta-Peptides

Grants and funding

This research was financially supported by grants from Nature Science Foundation of Jiangsu Province (BK20221051) and Postdoctoral Excellence Program of Jiangsu Province.