Many functions of glial cells depend on the formation of selective glial networks mediated by gap junctions formed by members of the connexin family. Olfactory ensheathing cells (OECs) are specialized glia associated with olfactory sensory neuron axons. Like other glia, they form selective networks, however, the connexins that support OEC connectivity in vivo have not been identified. We used an in vivo mouse model to selectively delete candidate connexin genes with temporal control from OECs and address the physiological consequences. Using this model, we effectively abolished the expression of connexin 43 (Cx43) in OECs in both juvenile and adult mice. Cx43‐deleted OECs exhibited features consistent with the loss of gap junctions including reduced membrane conductance, largely reduced sensitivity to the gap junction blocker meclofenamic acid and loss of dye coupling. This indicates that Cx43, a typically astrocytic connexin, is the main connexin forming functional channels in OECs. Despite these changes in functional properties, the deletion of Cx43 deletion did not alter the density of OECs. The strategy used here may prove useful to delete other candidate genes to better understand the functional roles of OECs in vivo.

A variety of glial cell functions are supported by connexin and pannexin proteins. These functions include the modulation of synaptic gain, the control of excitability through regulation of the ion and neurotransmitter composition of the extracellular milieu and the promotion of neuronal survival. Connexins and pannexins support these functions through diverse molecular mechanisms, including channel and non-channel functions. The former comprise the formation of gap junction-mediated networks supported by connexin intercellular channels and the formation of pore-like membrane structures or hemichannels formed by both connexins and pannexins. Non-channel functions involve adhesion properties and the participation in signaling intracellular cascades. Pathological conditions of the nervous system such as ischemia, neurodegeneration, pathogen infection, trauma and tumors are characterized by distinctive remodeling of connexin expression and function. However, whether these changes can be interpreted as part of the pathogenesis, or as beneficial compensatory effects, remains under debate. Here we review the available evidence addressing this matter with a special emphasis in mouse models with selective manipulation of glial connexin and pannexin proteins in vivo. We postulate that the beneficial vs. detrimental effects of glial connexin remodeling in pathological conditions depend on the impact of remodeling on the different connexin and pannexin channel and non-channel functions, on the characteristics of the inflammatory environment and on the type of interaction among glial cells types.

En un contexto de popularización y auge del uso e investigación de terapias psicodélicas en todo el mundo, el uso terapéutico de hongos psilocibios ha ganado masividad. Sus dos modalidades principales, las macrodosis (uso ocasional de dosis suficientes para producir efectos perceptuales, fisiológicos y psicológicos profundos) y las microdosis (uso de dosis suficientemente bajas como para permitir el desenvolvimiento de la persona en actividades cotidianas) se encuentran en desarrollo, tanto en investigaciones biomédicas tradicionales como en prácticas por parte de cultivadores, redes de usuaries y organizaciones vinculadas a la salud que utilizan o acompañan estas terapéuticas. Dichos desarrollos han mostrado resultados prometedores en el tratamiento de patologías ligadas principalmente a la salud mental. En el presente trabajo, indagamos sobre las experiencias terapéuticas con microdosis de hongos psilocibios en un colectivo de personas que realizó, durante el año 2022, esta terapia en un contexto de autoatención o en acompañamiento de organizaciones de salud alternativas en Argentina. Para ello, realizamos una encuesta anónima en la que se indagó sobre las motivaciones, formas de administración, y percepción sobre beneficios y dificultades de la terapia. Los resultados de la encuesta indican que les usuaries encuestades utilizan múltiples estrategias para acceder, administrarse y transitar la terapia, encontrando alivio para las patologías médicas por las que se acercan a la misma, pero también mejoras en su productividad y beneficios ligados a malestares no diagnosticados o a su calidad de vida en general. Esta investigación situada es el primer registro sistemático cualitativo de experiencias terapéuticas de usuaries con hongos psilocibios en Argentina y un aporte para valorizar estas prácticas de salud que funcionan y son realizadas en constante tensión con el sistema biomédico hegemónico y sus lógicas.