β-Endorphin Mediates Electroacupuncture-Induced Remyelination via Neural Stem Cell Lineage Modulation in Experimental Autoimmune Encephalomyelitis.

AIMS: Effective remyelination in multiple sclerosis (MS) requires both the proliferation of endogenous neural stem cells (NSCs) and their lineage-specific differentiation into oligodendrocyte progenitor cells (OPCs). This study aimed to investigate whether electroacupuncture (EA) promoted NSC proliferation and OPC differentiation via β-endorphin (β-EP)-mediated opioid signaling in a murine model of MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice to model MS. EA stimulation was applied daily at the Zusanli (ST36) acupoint. NSC proliferation and OPC differentiation were assessed via immunofluorescence, flow cytometry (FCM), and RT-qPCR. β-EP expression and opioid receptor involvement were evaluated in the hypothalamus and subventricular zone (SVZ). Naloxone, a nonselective opioid receptor antagonist, was used to determine the role of opioid signaling in EA-induced effects. RESULTS: EA significantly enhanced NSC proliferation and increased the proportion of NSC-derived OPCs in the SVZ of EAE mice. EA treatment improved clinical score, reduced demyelination, and attenuated leukocyte infiltration of the central nervous system (CNS). Mechanistically, EA upregulated β-EP and its precursor pro-opiomelanocortin (POMC), along with opioid receptors μ-opioid receptor (MOR) and κ-opioid receptor (KOR) (encoded by Oprm1 and Oprk1, respectively). Naloxone administration abolished the beneficial effects of EA on NSC behavior and remyelination, confirming the involvement of opioid receptor-dependent β-EP signaling. CONCLUSION: EA promotes remyelination in EAE mice by stimulating β-EP-mediated NSC proliferation and OPC differentiation. These findings reveal a novel neuroregenerative mechanism and support EA as a promising adjunctive strategy for demyelinating diseases such as MS.