Cocaine-Induced Microglial Impairment and Its Rehabilitation by PLX-PAD Cell Therapy

Abstract

Chronic cocaine use triggers inflammatory and oxidative processes in the central nervous system, resulting in impaired microglia. Mesenchymal stem cells, known for their immunomodulatory properties, have shown promise in reducing inflammation and enhancing neuronal survival. The study employed the cocaine self-administration model, focusing on ionized calcium-binding adaptor protein 1 (Iba-1) and cell morphology as markers for microglial impairment and PLX-PAD cells as a treatment for attenuating cocaine craving. The results revealed an addiction-stage and region-specific impairment in microglia following chronic cocaine exposure, with deficits observed in the Nucleus Accumbens (NAc) during the maintenance stage and in both the NAc and Dentate Gyrus (DG) during the extinction and reinstatement stages. Furthermore, PLX-PAD cell therapy demonstrated a significant reduction in cocaine craving and seeking behavior, interestingly accompanied by the prevention of Iba-1 level decrease and restoration of microglial activity in the NAc and DG. These findings highlight the unique role of microglia in modulating cocaine addiction behaviors through their influence on synaptic plasticity and neuronal remodeling associated with memory formation. They also suggest that PLX-PAD therapy may mitigate the detrimental effects of chronic cocaine exposure on microglia, underscoring the importance of incorporating microglia in comprehensive addiction rehabilitation strategies.