NLRP3 inflammasome activation underlies the neuro-oxidative stress associated with Methamphetamine (METH) and SARS-CoV2 induced co-morbidity in human microglia

Abstract

Abstract Acute and chronic use of Methamphetamine (METH) has critical immunological implications and METH users are more vulnerable to SARS-CoV2 infection. Inflammasomes are activated in response to SARS-CoV2 infection. METH also activates NLRP3 inflammasome in microglia and promotes neuro cognitive deficits. The goal of the study was to examine the involvement of NLRP3 inflammasome in METH and/or SARS-CoV2 induced neuro-oxidative stress in microglial cells. Our results suggests that METH +/− SARS-CoV2 initiated a neuro immune-inflammatory response and mitochondrial oxidative stress via NLRP3 inflammasome activation induced increased Caspase −1 and increased lipid peroxidation. Our data suggests that SARS-CoV2 infection in METH abusing subjects may result in long-term neurological deficits resulting from microglial dysfunction and apoptosis attributed to NLRP3 inflammasome activation.