Paclitaxel induces region-specific microglial remodeling associated with chronic behavioral deficits and modulated by electroacupuncture in rats

Chemotherapy-associated behavioral deficits, including cognitive impairment and depression, collectively termed chemobrain, often persist into the chronic phase after treatment, yet their underlying cellular mechanisms remain unclear. In particular, it remains unknown whether long-lasting behavioral deficits are associated with sustained neuroinflammatory responses or other forms of microglial alteration. We therefore examined whether chronic behavioral deficits were associated with region-specific microglial morphological alterations and inflammatory gene expression changes, and how EA intervention was associated with these alterations. Male SD rats were assigned to the Control, PTX, and PTX + EA groups. Cognitive and emotional behaviors were assessed using behavioral tests. Microglial morphology in the hippocampus across the dorsoventral axis and mPFC was analyzed using skeleton analysis, and inflammatory gene expression was evaluated by qPCR. PTX induced cognitive impairment and depressive-like behavior, accompanied by a selective reduction in microglial process number and length in the dentate gyrus of the dorsal hippocampus and the infralimbic cortex of the mPFC. Microglial morphology differed between the PTX and PTX + EA groups in both regions, although the difference in the dorsal dentate gyrus was limited to process number. No significant changes in the inflammatory genes examined were detected in the hippocampus or mPFC. Thus, PTX produced chronic behavioral deficits accompanied by selective microglial remodeling in the dorsal dentate gyrus and infralimbic cortex, but not in the ventral hippocampus, with no detectable changes in inflammatory gene expression. Behavioral outcomes and microglial morphology differed between the PTX and PTX + EA groups, indicating an association between EA intervention and region-specific microglial remodeling.