Observational analysis reveals cognitive dysfunction in mice exposed to methamphetamine, suggesting neuroinflammation involvement.
More than half of chronic methamphetamine (METH) users exhibit multi-domain cognitive deficits, including impaired attention, executive function, and memory. MRI studies consistently demonstrate hippocampal atrophy and frontotemporal cortical thinning; these structural changes spatially overlap with glial activation, indicating the coexistence of morphological damage and ongoing neuroinflammation. To clarify causality, we developed a mouse model in which low-dose METH is micro-infused into the nucleus accumbens. The mice displayed cognitive dysfunction and hippocampal long-term potentiation deficits together with microglial activation and mRNA up-regulation of IL-1β and the complement component C1q. Suppressing microglial activation with minocycline normalized these soluble factors and restored cognitive function. Complement proteins drive microglia-mediated synaptic pruning, and their over-activation has been implicated in Alzheimer's disease and schizophrenia. Taken together, our findings suggest that METH-induced cognitive impairment is mediated by abnormal microglial pruning via complement signaling. This review summarizes the clinical phenotype of METH-related cognitive dysfunction, integrates preclinical findings, and proposes novel therapeutic avenues that target microglial activation.
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