Microglia NLRP3 Inflammasome and Neuroimmune Signaling in Substance Use Disorders

Abstract

During the last decade, substance use disorders (SUDs) have been increasingly recognized as neuroinflammation-related brain diseases. Various types of abused drugs (cocaine, methamphetamine, alcohol, opiate-like drugs, marijuana, etc.) can modulate the activation status of microglia and neuroinflammation levels which are involved in the pathogenesis of SUDs. Several neuroimmune signaling pathways, including TLR/NF-кB, reactive oxygen species, mitochondria dysfunction, as well as autophagy defection, etc., have been implicated in promoting SUDs. Recently, inflammasome-mediated signaling has been identified as playing critical roles in the microglia activation induced by abused drugs. Among the family of inflammasomes, NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) serves the primary research target due to its abundant expression in microglia. NLRP3 has the capability of integrating multiple external and internal inputs and coordinately determining the intensity of microglia activation under various pathological conditions. Here, we summarize the effects of abused drugs on NLRP3 inflammasomes, as well as others, if any. The research on this topic is still at an infant stage; however, the readily available findings suggest that NLRP3 inflammasome could be a common downstream effector stimulated by various types of abused drugs and play critical roles in determining abused-drug-mediated biological effects through enhancing glia–neuron communications. NLRP3 inflammasome might serve as a novel target for ameliorating the development of SUDs.

Alcohol and the Brain–Gut Axis: The Involvement of Microglia and Enteric Glia in the Process of Neuro-Enteric Inflammation

“…These cells are localized in different tissues as specialized cells, for example, as microglia and enteric glial cells in the brain and gut, respectively. These tissue-specific resident cells manifest distinct and unique characteristics and play important roles in the host immune defense system in response to alcohol [163,164]. During alcohol-induced neuroinflammation, microglia become activated and contribute to the modulation of a number of cytokines, including TNFα, which act as messengers to trigger a downstream cascade of signaling molecules.…”

Effects of unburned tobacco smoke on inflammatory and oxidative mediators in the rat prefrontal cortex

“…The prefrontal cortex (PFC) is one of the brain regions mostly affected by traditional tobacco smoking ( Karama et al, 2015 ) and plays a crucial role in the reward circuitry activated by drugs of abuse, including nicotine ( Goldstein and Volkow, 2011 ). On this base and taking into account the role of oxidative and inflammatory process in substance use disorder development ( Zhang et al, 2018 ; McGrath and Briand, 2019 ; Johnstone et al, 2021 ; Guo et al, 2023 ), the present study aimed to investigate the neurotoxic effects induced by the exposure to the HnB tobacco stick mainstream and likely associated with tobacco dependence in the rat PFC. In particular, the generation of reactive radical species (RRS) and the perturbation of antioxidant and DNA repair enzymatic machinery were assessed.…”