Namdev S. Togre , Priyanka S. Bhoj , Naveen Mekala, Rebecca Hancock, Jayshil Trivedi, Yuri Persidsky
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引用次数: 0
Abstract
Chronic alcohol consumption is a major risk factor for neuroinflammation and cognitive decline, yet the molecular underpinnings connecting peripheral alcohol-induced injury to central nervous system (CNS) dysfunction remain poorly defined. Emerging evidence implicates purinergic P2X7 receptor (P2X7R) signaling and extracellular vesicles (EVs) as key mediators in peripheral–central communication. Ethanol exposure promotes oxidative stress, mitochondrial dysfunction, and blood–brain barrier (BBB) disruption, leading to sustained microglial activation and neuronal injury. Concurrently, alcohol-induced damage in the gut, liver, and lung, triggers systemic inflammation and EV release. These EVs, enriched in proinflammatory cytokines, miRNAs, mitochondrial DNA, and other DAMPs, can cross the compromised BBB and engage innate immune receptors, such as TLR4 and P2X7R, on glial cells, amplifying neuroimmune responses.
In this review, we integrated recent findings on EV biogenesis, P2X7R signaling, and neurovascular dysfunction in the context of alcohol use disorder. We proposed a mechanistic model in which ethanol-triggered P2X7R activation drives EV release, turning these vesicles into inflammatory couriers that carry peripheral injury signals to the brain. We emphasize EV cargo as promising biomarkers of alcohol-related neurodegeneration and explore emerging therapies that target EV pathways or P2X7R to curb alcohol-induced CNS damage.
期刊介绍:
Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals.
As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.