RESUMEN
Growing evidence suggests that glial cells express virtually all known types of neurotransmitter receptors, enabling them to sense neuronal activity and microenvironment changes by responding locally via the Ca(2+)-dependent release of bioactive molecules, known as "gliotransmitters". Several mechanisms of gliotransmitter release have been documented. One of these mechanisms involves the opening of plasma membrane channels, known as hemichannels. These channels are composed of six protein subunits consisting of connexins or pannexins, two highly conserved protein families encoded by 21 or 3 genes, respectively, in humans. Most data indicate that under physiological conditions, glial cell hemichannels have low activity, but this activity is sufficient to ensure the release of relevant quantities of gliotransmitters to the extracellular milieu, including ATP, glutamate, adenosine and glutathione. Nevertheless, it has been suggested that dysregulations of hemichannel properties could be critical in the beginning and during the maintenance of homeostatic imbalances observed in several brain diseases. In this study, we review the current knowledge on the hemichannel-dependent release of gliotransmitters in the physiology and pathophysiology of the CNS.
Asunto(s)
Encéfalo/metabolismo , Conexinas/metabolismo , Neuroglía/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Humanos , Neuronas/metabolismo , Transducción de Señal , Transmisión SinápticaRESUMEN
HIV is a major public health issue, and infection of CD4(+) T lymphocytes is one of its key features. Whereas several cellular proteins have been identified that facilitate viral infection and replication, the role of hemichannels in these processes has not been fully characterized. We now show that the HIV isolates, R5 and X4, induced a transient-early (5-30 min) and a later, persistent (48-120 h) opening of Panx1 hemichannels, which was dependent on the binding of HIV to CD4 and CCR5/CXCR4 receptors. Blocking Panx1 hemichannels by reducing their opening or protein expression inhibited HIV replication in CD4(+) T lymphocytes. Thus, our findings demonstrate that Panx1 hemichannels play an essential role in HIV infection.
Asunto(s)
Linfocitos T CD4-Positivos/virología , Conexinas/fisiología , VIH/fisiología , Proteínas del Tejido Nervioso/fisiología , Conexina 43/fisiología , Humanos , Receptores CCR5/fisiología , Receptores CXCR4/fisiología , Replicación ViralRESUMEN
Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.
Asunto(s)
Conducta Animal/fisiología , Condicionamiento Clásico/fisiología , Neuronas/patología , Estrés Psicológico/patología , Estrés Psicológico/fisiopatología , Estimulación Acústica , Animales , Reacción de Prevención/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Estimulación Luminosa , Ratas , Ratas Sprague-DawleyRESUMEN
Aqueous and alcoholic extracts of pods and flowers of Tecoma sambucifolia H.B.K. (Bignoniaceae) ('huarumo') were analysed to determine their anti-inflammatory activity (carrageenan-induced edema test), antinociceptive activity (acetic acid writhing test) and 'in vitro' toxicity in Chinese hamster ovary cells, human hepatome cells and human larynx epidermal carcinoma cells. The cytotoxic effects of both extracts were evaluated by two endpoint systems: neutral red uptake assay and tetrazolium assay. The results showed that all extracts have anti-inflammatory and antinociceptive activity, but the highest potency is that of the alcoholic extracts. There were significant differences in cytotoxicity between extracts and among the response of cells to them. The highest cytotoxicity was noted with the alcoholic extract, and the human hepatome cell line was the most sensitive, especially to the alcoholic extract of flowers. The aqueous pod extract appeared to have the best pharmaco-toxicological profile, since it provided a significant reduction of both pain and inflammation together with the lowest cytotoxicity.