Abstract

Chronic neuroinflammation, characterized by the persistent activation of microglia into a pro-inflammatory (M1) phenotype, is a critical driver of neurodegeneration and cognitive decline in the aging brain. This study investigates the therapeutic potential of Ethylmethylhydroxypyridine Succinate (EMHPS), a known neuroprotector, to modulate microglial polarization in an aging rat model. The objective was to determine if EMHPS could shift the microglial balance towards an anti-inflammatory (M2) state, thereby mitigating age-related neuroinflammation. Aging rats were administered EMHPS, and microglial phenotypes in the cerebral cortex were analyzed using immunohistochemistry and gene expression profiling of M1 (e.g., iNOS, TNF-α) and M2 (e.g., Arg-1, IL-10) markers. Our findings demonstrate that EMHPS treatment significantly increased the expression of M2 markers and reduced M1 marker expression, confirming the induction of an anti-inflammatory microglial polarization. This effect is hypothesized to be mediated by the succinate moiety of the compound, potentially activating the succinate receptor SUCNR1 and influencing mitochondrial metabolism. These results highlight EMHPS as a promising pharmacological agent for targeting microglial dysfunction and chronic neuroinflammation, offering a novel therapeutic strategy for age-related neurological disorders.