title: Restraint stress increases hemichannel activity in hippocampal glial cells and neurons.
abstract: Stress affects brain areas involved in learning and emotional responses, which may contribute in the development of cognitive deficits associated with major depression. These effects have been linked to glial cell activation, glutamate release and changes in neuronal plasticity and survival including atrophy of hippocampal apical dendrites, loss of synapses and neuronal death. Under neuro-inflammatory conditions, we recently unveiled a sequential activation of glial cells that release ATP and glutamate via hemichannels inducing neuronal death due to activation of neuronal NMDA/P2X7 receptors and pannexin1 hemichannels. In the present work, we studied if stress-induced glia activation is associated to changes in hemichannel activity. To this end, we compared hemichannel activity of brain cells after acute or chronic restraint stress in mice. Dye uptake experiments in hippocampal slices revealed that acute stress induces opening of both Cx43 and Panx1 hemichannels in astrocytes, which were further increased by chronic stress; whereas enhanced Panx1 hemichannel activity was detected in microglia and neurons after acute/chronic and chronic stress, respectively. Moreover, inhibition of NMDA/P2X7 receptors reduced the chronic stress-induced hemichannel opening, whereas blockade of Cx43 and Panx1 hemichannels fully reduced ATP and glutamate release in hippocampal slices from stressed mice. Thus, we propose that gliotransmitter release through hemichannels may participate in the pathogenesis of stress-associated psychiatric disorders and possibly depression.
authors.affiliation: Departamento de Neurología, Escuela de Medicina, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Orellana
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Moraga-Amaro
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello Santiago, Chile.
authors.forename: Raúl
authors.initials: R
authors.lastname: Díaz-Galarce
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello Santiago, Chile.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Rojas
authors.affiliation: Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Carola J
authors.initials: CJ
authors.lastname: Maturana
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Facultad de Ciencias Biológicas and Facultad de Medicina, Universidad Andres Bello Santiago, Chile.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Stehberg
authors.affiliation: Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile Santiago, Chile ; Instituto Milenio, Centro Interdisciplinario de Neurociencias de Valparaíso Santiago, Chile.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Sáez
keywords: connexins; glia; hemichannels; hippocampus; neuron; pannexins; stress