Astrocytes are electrically nonexcitable cells that communicate by means of Ca(2+) signaling. Long-distance intercellular Ca(2+) waves are initiated by release of ATP and activation of purinergic ...receptors on nearby cells. Previous studies have implicated connexin 43 (Cx43) in ATP release, but definitive proof that ATP exits through Cx43 hemichannels does not exist. Here, through several alternative approaches, we show that ATP anions can permeate through Cx43 hemichannels. First, openings of Cx43 hemichannels were detected in both cell-attached and inside-out patch recordings in C6 cells expressing Cx43, but not in C6 cells expressing Cx43-eGFP (enhanced green fluorescent protein) or a C-terminus truncation mutant of Cx43. Second, Cx43 hemichannel openings were inhibited by three structurally different gap-junction channel blockers, but not by the P2X(7) blocker Brilliant blue G. Third, bioluminescence imaging of ATP combined with single-channel recording in the inside-out patch configuration showed that ATP efflux coincided with channel openings and was absent when the Cx43 hemichannel was closed. Fourth, ion replacement experiments confirmed that Cx43 hemichannels are permeable to ATP. In summary, these observations provide the first direct evidence for efflux of ATP through Cx43 hemichannels. Furthermore, a putative Cx43 hemichannel with characteristics identical to the Cx43 hemichannel in C6 cells was identified in the membrane of hippocampal astrocytes in acutely prepared slices.
Aquaporin-4 (AQP4) is a primary influx route for water during brain edema formation. Here, we provide evidence that brain swelling triggers Ca²⁺ signaling in astrocytes and that deletion of the Aqp4 ...gene markedly interferes with these events. Using in vivo two-photon imaging, we show that hypoosmotic stress (20% reduction in osmolarity) initiates astrocytic Ca²⁺ spikes and that deletion of Aqp4 reduces these signals. The Ca²⁺ signals are partly dependent on activation of P2 purinergic receptors, which was judged from the effects of appropriate antagonists applied to cortical slices. Supporting the involvement of purinergic signaling, osmotic stress was found to induce ATP release from cultured astrocytes in an AQP4-dependent manner. Our results suggest that AQP4 not only serves as an influx route for water but also is critical for initiating downstream signaling events that may affect and potentially exacerbate the pathological outcome in clinical conditions associated with brain edema.
Spinal cord injury (SCI) is often complicated by secondary injury as a result of the innate inflammatory response to tissue trauma and swelling. Previous studies have shown that excessive ATP release ...from peritraumatic regions contributes to the inflammatory response to SCI by activation of low-affinity P2X7 receptors. Because connexin hemichannels constitute an important route for astrocytic ATP release, we here evaluated the impact on post-traumatic ATP release of deletion of connexins (Cx30/Cx43) in astrocytes. In vivo bioluminescence imaging showed a significant reduction in ATP release after weight-drop injury in mice with deletion of Cx43 compared with Cx43-expressing littermates, both on a Cx30 knockout background. Moreover, astrogliosis and microglia activation were reduced in peritraumatic areas of those mice lacking Cx43; motor recovery was also significantly improved, and the traumatic lesion was smaller. Combined, these observations are consistent with a contribution by astrocytic hemichannels to post-traumatic ATP release that aggravates secondary injury and restrains functional recovery after experimental spinal cord injury. Connexins may thereby constitute a new therapeutic target in spinal cord injury.
The Apoptosis is an intensely studied mechanism for cancer therapy. Various genes, drugs, and molecules have been combined to potentiate the apoptotic effect against tumor cells. Magnetic ...nanocomplexes with biopolymers have been proposed as nanocarriers for delivery of active molecules and improve apoptosis induction. To these purpose were formulated magnetic nanoparticles with curcumin coated chitosan (MNPs-CHI-TPP-CUR) and magnetic nanoparticles with pCEM-TRAIL plasmid coated chitosan (MNPs-CHI-TPP-TRAIL) for use alone or in combination to induce the apoptosis of
B16F10
tumor cells because curcumin is capable of overexpressing receptors TRAIL required for apoptosis induction. Also, curcumin (CUR) has been used as a photosensitizer in photodynamic therapy (PDT). In this work, it was produced and characterized nanoparticles with curcumin and nanoparticles with TRAIL gene. Both types of nanoparticles were ~ 200 nm size. The results showed that the combination of (MNPs-CHI-TPP-CUR) and (MNPs-CHI-TPP-TRAIL) induced a significant increase in cellular death within 48 h compared with the effect of each nanocomplex individually, demonstrating a synergic effect. This is the first description the synergic interaction between TRAIL gene and curcumin drug to improve the apoptosis in cancer cells. Also, it was determined that cellular death was potentiated when the treated cells were exposed to laser photoactivation with wavelengths of 405 nm and 532 nm for 15 min.
Graphical abstract
Objective:
This article aimed to summarize our clinical experience with a standardized tonsil-sparing transoral surgical approach used for treatment of styloid process-carotid artery Eagle’s ...syndrome.
Methods:
Eleven consecutive patients, from 2007 to 2013, underwent surgical treatment to remove elongated styloid apophyses transorally. Outcomes were assessed in terms of intraoperative and postoperative complications and patients’ evolution.
Results:
No patient experienced any intraoperative or postoperative complications. All patients have been followed up to present and 10 of them have shown complete relief of the symptoms and improvement of functional ability.
Conclusion:
The tonsil-sparing transoral surgical approach described is suitable for treating patients with elongated styloid apophyses.
Preconditioning is an endogenous mechanism in which a nonlethal exposure increases cellular resistance to subsequent additional severe injury. Here we show that connexin 43 (Cx43) plays a key role in ...protection afforded by preconditioning. Cx43 null mice were insensitive to hypoxic preconditioning, whereas wild-type littermate mice exhibited a significant reduction in infarct volume after occlusion of the middle cerebral artery. In cultures, Cx43-deficient cells responded to preconditioning only after exogenous expression of Cx43, and protection was attenuated by small interference RNA or by channel blockers. Our observations indicate that preconditioning reduced degradation of Cx43, resulting in a marked increase in the number of plasma membrane Cx43 hemichannels. Consequently, efflux of ATP through hemichannels led to accumulation of its catabolic product adenosine, a potent neuroprotective agent. Thus, adaptive modulation of Cx43 can offset environmental stress by adenosine-mediated elevation of cellular resistance.
Defining the pathways through which neurons and astrocytes communicate may contribute to the elucidation of higher central nervous system functions. We investigated the possibility that decreases in ...extracellular calcium ion concentration (Ca(2+)(e)) that occur during synaptic transmission might mediate signaling from neurons to glia. Using noninvasive photolysis of the photolabile Ca(2+) buffer diazo-2 {N-2-2-2-bis(carboxymethyl)amino-5-(diazoacetyl)phenoxyethoxy-4-methylphenyl-N-(carboxymethyl)-, tetrapotassium salt} to reduce Ca(2+)(e) or caged glutamate to simulate glutamatergic transmission, we found that a local decline in extracellular Ca(2+) triggered astrocytic adenosine triphosphate (ATP) release and astrocytic Ca(2+) signaling. In turn, activation of purinergic P2Y1 receptors on a subset of inhibitory interneurons initiated the generation of action potentials by these interneurons, thereby enhancing synaptic inhibition. Thus, astrocytic ATP release evoked by an activity-associated decrease in Ca(2+)(e) may provide a negative feedback mechanism that potentiates inhibitory transmission in response to local hyperexcitability.
El granuloma eosinofílico es la forma localizada de la histiocitosis de células de Langerhans. Es una rara enfermedad que puede simular un proceso infeccioso del oído medio y áreas vecinas, ...especialmente en la población pediátrica. Se presenta caso clínico de una adolescente con enfermedad de histiocitosis de Langerhans monofocal en hueso temporal. Su diagnóstico presentó dificultades inherentes a su presentación clínica y a los estudios anatomopatológicos. La respuesta al tratamiento con radioterapia a dosis bajas fue satisfactoria.
Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including ...obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individuals with surgically implanted stimulation electrodes, the cellular pathways involved in mediating the effects of DBS remain unknown. Here we show that DBS is associated with a marked increase in the release of ATP, resulting in accumulation of its catabolic product, adenosine. Adenosine A1 receptor activation depresses excitatory transmission in the thalamus and reduces both tremor- and DBS-induced side effects. Intrathalamic infusion of A1 receptor agonists directly reduces tremor, whereas adenosine A1 receptor-null mice show involuntary movements and seizure at stimulation intensities below the therapeutic level. Furthermore, our data indicate that endogenous adenosine mechanisms are active in tremor, thus supporting the clinical notion that caffeine, a nonselective adenosine receptor antagonist, can trigger or exacerbate essential tremor. Our findings suggest that nonsynaptic mechanisms involving the activation of A1 receptors suppress tremor activity and limit stimulation-induced side effects, thereby providing a new pharmacological target to replace or improve the efficacy of DBS.
Introducción: la falta de articulación de las neurociencias a los procesos educativos dio origen a una serie de conceptos erróneos conocidos como neuromitos, falacias que pueden ser asumidas por ...desconocimiento formal crítico de la manera en que funciona el sistema nervioso. Este artículo se propuso describir, en primer lugar, aspectos de la enseñanza del sistema nervioso y las percepciones sobre los neuromitos que tienen docentes de Ciencias Naturales en educación básica. Metodología: para ello, se aplicó una encuesta en línea a 20 docentes de Ciencias Naturales que se desempeñan en la educación básica en el contexto colombiano. Resultados y discusión: se encontró que la mayoría de los docentes abordan los contenidos del sistema nervioso desde la exploración de saberes previos hasta el desarrollo de procesos complejos de la anatomía y la fisiología. Por otra parte, si bien la mayoría de los docentes no está de acuerdo con los neuromitos planteados, aún persisten: los periodos críticos, la dominancia hemisférica y el uso del 10 % del cerebro. En este sentido, se reconoce que la prevalencia de neuromitos en docentes puede tener repercusiones en procesos educativos y evidencia la brecha aún existente entre la neurociencia y la educación. Conclusiones: de acuerdo con lo anterior, es necesario que desde los programas de formación de docentes y las instituciones educativas se abran espacios de reflexión crítica que permitan a los docentes y directivos docentes acceder a información relacionada con los avances científicos y tecnológicos entre neurociencia y educación.
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