[Microglia-mediated cognitive impairment induced by methamphetamine]

Area of Science:

• Neuroscience
• Neuroinflammation
• Neuropharmacology

Background:

• Chronic methamphetamine (METH) use is linked to cognitive deficits and brain structural changes.
• Neuroinflammation, indicated by glial activation, co-occurs with morphological damage in METH users.
• Microglial activation and complement signaling are implicated in neurodegenerative and psychiatric disorders.

Purpose of the Study:

• To investigate the causal link between METH, neuroinflammation, and cognitive dysfunction.
• To explore the role of microglial activation and complement signaling in METH-induced cognitive impairment.
• To identify potential therapeutic targets for METH-related cognitive deficits.

Main Methods:

• Developed a mouse model with nucleus accumbens micro-infusion of low-dose METH.
• Assessed cognitive function, hippocampal long-term potentiation, and microglial activation markers (IL-1β, C1q).
• Administered minocycline to suppress microglial activation and evaluated its effects.

Main Results:

• METH-infused mice exhibited cognitive deficits and impaired hippocampal long-term potentiation.
• These mice showed increased microglial activation and elevated IL-1β and C1q mRNA levels.
• Minocycline treatment normalized these molecular markers and restored cognitive function.

Conclusions:

• METH-induced cognitive impairment is mediated by abnormal microglial pruning via complement signaling.
• Targeting microglial activation presents a promising therapeutic strategy for METH-related cognitive dysfunction.
• This study provides a preclinical basis for developing novel treatments for stimulant use disorder.