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Updated: Jan 15, 2026
Author Spotlight: Creating a Versatile Experimental Autoimmune Encephalomyelitis Model Relevant for Both Male and Female Mice
Published on: October 13, 2023
Neuroprotective role of allopregnanolone in alleviating depression-like behaviors by modulating brain function in
Shujia Song1, Tao Wang2, Linwen Liu3
1Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Background:
Depression is among the most common comorbidities associated with MS, significantly impairing patients' quality of life and prognosis. In this study, we investigated the therapeutic effects of allopregnanolone (AP) on depression-like behaviors in a rat model of MS.
Methods:
Female Lewis rats (6-8 weeks old, 160-180g) were used to establish the rat model of experimental autoimmune encephalomyelitis (EAE). The behavioral tests evaluated depression-like behaviors. The intrinsic activity in the brain were assessed using functional magnetic resonance imaging (fMRI). For pathological and molecular expression detection, hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) was used to evaluated hormones and inflammatory cytokines.
Results:
The hypothalamus-pituitary-gonad (HPG) axis was inhibited while the hypothalamus-pituitary-adrenal (HPA) axis was activated in EAE rats. Progesterone and its derivate, AP, were involved in the mechanism of depression-like behaviors in EAE. Exogenous AP increased the mechanical withdrawal threshold, sucrose preference in the SPT, the percentage of time in open arm in the EPM, and decreased the immobility time in the FST. The depression-related brain regions showed decreased fALFF and ReHo in EAE rats with altered functional connectivity, and AP also partly reversed changes in these brain regions. AP could reduce inflammatory cytokines and alleviate inflammation induced by EAE.
Conclusion:
The inhibition of HPG axis played an important role in mechanism of EAE-induced depression-like behaviors. AP played neuroprotective effects in relieving EAE-induced depression-like behaviors. AP ameliorated functional changes in specific brain regions.
