Cocaine-mediated microglial activation involves the ER stress-autophagy axis

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Cocaine abuse is linked to neuroinflammation and neurodegeneration, particularly in advanced HIV-1 infection.
• Autophagy is crucial for immune responses, but its connection to cocaine use was unexplored.

Purpose of the Study:

• To investigate the functional link between cocaine exposure and autophagy in microglial cells.
• To explore the role of autophagy in cocaine-induced neuroinflammation.

Main Methods:

• Assessed autophagy markers (BECN1, ATG5, MAP1LC3B) in BV-2 and primary rat microglial cells after cocaine exposure.
• Utilized autophagy inhibitors (3-MA, wortmannin) and ER stress inhibitors (salubrinal) for mechanistic studies.
• Validated findings in vivo using cocaine-treated mouse brains and measured inflammatory factor release.

Main Results:

• Cocaine dose- and time-dependently induced autophagy markers in microglial cells.
• Cocaine-induced autophagy involved upstream endoplasmic reticulum (ER) stress pathways.
• In vivo studies confirmed increased autophagy in cocaine-treated mouse brains.
• Inhibition of autophagy reduced cocaine-mediated microglial activation and inflammatory factor release.

Conclusions:

• Cocaine exposure induces autophagy in microglial cells, closely associated with neuroinflammation.
• Autophagy plays a significant role in cocaine-induced microglial activation.
• Targeting autophagy presents a potential therapeutic avenue for cocaine-related neuroinflammatory conditions.