Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage.

Autor: Gómez GI; Institute of Biomedical Sciences, Faculty of Health Sciences, Universidad Autónoma de Chile, Santiago, Chile., Alvear TF; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile., Roa DA; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile., Farias-Pasten A; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile., Vergara SA; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile., Mellado LA; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile., Martinez-Araya CJ; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile., Prieto-Villalobos J; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile., García-Rodríguez C; Instituto de Neurociencia, Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, 2360102, Chile., Sánchez N; Department of Anatomy, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile., Sáez JC; Instituto de Neurociencia, Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, 2360102, Chile., Ortíz FC; Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Mechanisms of Myelin Formation and Repair Laboratory, Chacabuco 675, of. 212, Santiago, 8350347, Chile. fernando.ortiz.c@usach.cl., Orellana JA; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile. jaorella@uc.cl.
Jazyk: angličtina
Zdroj: Biological research [Biol Res] 2024 Apr 04; Vol. 57 (1), pp. 15. Date of Electronic Publication: 2024 Apr 04.
DOI: 10.1186/s40659-024-00493-2
Abstrakt: Background: Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated.
Results: Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1β and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival.
Conclusion: Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: