CB2 receptors in neurons of the central nervous system

The endocannabinoid system is formed by endogenous ligands, biosynthetic enzymes and two classical receptors: CB1 and CB2. From a classical point of view, CB1 receptors are the “central cannabinoid receptors” expressed in neurons, whose function is the regulation of neurotransmitter release. On the other hand, CB2 receptors are considered the “peripheral cannabinoid receptors”, expressed in peripheral tissues. However, this classical view has changed over the years; new endogenous ligands, receptors isoform variants, new cellular locations such as mitochondria and new putative receptors GPR119 and GPR55 have been described. Thus, evidence indicates that the endocannabinoid system is more complex than once thought. In this regard, over the years, CB2R were found in glial cells where they modulate immune response; moreover, with the development of more selective ligands, antibodies and the characterization of their genes, the expression of CB2R in central neurons became evident. Thus, several questions arise concerning these findings. What is the function of these receptors in neurons? Do they also control the release of neurotransmitters and others? Here we review the state of the art for these findings and the possible future direction of this new line of research that contributes to understanding the complexity of the endocannabinoid system.El sistema endocanabinoide está formado por sus ligandos endógenos, enzimas biosintéticas y dos receptores clásicos denominados CB1 y CB2. Clásicamente el RCB1 es el “receptor canabinoide central” expresado en neuronas, que regula la liberación de neurotransmisores en la plasticidad sináptica. Por otro lado, el RCB2 es el “receptor canabinoide periférico” expresado en el sistema inmune. Sin embargo, esta visión clásica ha cambiado con los años; nuevos ligandos endógenos, isoformas de los receptores, nuevas localizaciones celulares como la mitocondria, y nuevos receptores putativos: GPR119 y GPR55 han sido propuestos. Así, el sistema endocanabinoide es más complejo de lo que se pensaba. Al paso del tiempo, los RCB2 se encontraron en las células gliales donde modulan la respuesta en casos de insulto, más todavía con el desarrollo de ligandos más selectivos, anticuerpos y caracterización de sus genes, la expresión de RCB2 en neuronas centrales se hizo evidente. Así, diversas preguntas surgieron de estos hallazgos. ¿Cuál es la función de estos receptores en las neuronas? ¿Controlan la liberación de neurotransmisores? Y otras más. En esta revisión mostramos el estado del arte de estos hallazgos y la dirección futura de esta línea de investigación que contribuirá a entender la complejidad del sistema endocanabinoide.Sociedad Argentina de Fisiologí

Molecular Processing of Tau Protein in Progressive Supranuclear Palsy : Neuronal and Glial Degeneration

ACKNOWLEDGMENTS This work was supported by Fondo Nacional de Ciencia y Tecnologia, FONDOCyT, from the Ministry of Higher Education, Science and Technology, Dominican Republic (2015-3A2-127 to MP-H) and (2018-2019-2A3-208 to JL-M and MP-H). The authors want to express their gratitude to the following: Dr. P. Davies† (Albert Einstein College of Medicine, Bronx, NY, USA) and Lester I. Binder† (North Western, Chicago, IL, USA) for the generous gift of mAbs TG–3 and Alz–50, and Tau–1, Tau–5 and Tau–7, respectively; Tec. Amparo Viramontes Pintos for the handling of the brain tissue; support in the confocal microscopy unit of CIIDIR Durango, Instituto Politecnico Nacional; Union Medica Uni- A. Mart´ınez-Maldonado et al. / Molecular Processing of Tau Protein in Progressive Supranuclear Palsy 1529 versity Clinic, Dominican Republic, for their support and collaboration in the development of this research project. We also want to express our gratitude to the Mexican families who have donated the brain of their loved ones affected with Alzheimer’s disease and made our research possible. This work is dedicated to the memory of Professor Dr. Jose Ra ´ ul Mena L ´ opez ´ †. †Deceased. Authors’ disclosures available online (https:// www.j-alz.com/manuscript-disclosures/20-1139r2).Peer reviewedPublisher PD

El conocimiento que tienen las adolescentes femeninas de 12 a 19 años de edad para afrontar un embarazo a temprana edad en el Centro de Salud, Maternidad Periférica 1o de Julio, Ciudad de Guatemala, durante 2012.

Aporta conocimientos a las adolescentes femeninas que asisten al Centro de Salud, Maternidad Periférica de la colonia 1ro de Julio de la ciudad de Guatemala. Determina la importancia de promover la educación sexual para evitar embarazos a temprana edad. La investigación se realizó durante el año 2012. La muestra estuvo representada por 30 adolescentes femeninas, comprendidas entre los 12 – 19 años de edad. Para seleccionar la muestra se utilizó la técnica de muestreo no aleatoria. La recopilación de datos se realizó por medio de las técnicas siguientes Técnicas: entrevistas estructuradas, un programa donde se aplicó un cuestionario, y la evaluación del taller. Analiza e interpreta los resultados y concluye que, las adolescentes se convierten en madres a temprana edad, aunque no lo desean, debido a la falta orientación o información inadecuada que reciben sobre educación sexual. Recomienda, para ayudar a las adolescentes a evitar los embarazos no planificados, se necesita aumentar los niveles de orientación e información sobre educación sexual e implementar estrategias educativas para las adolescentes, tanto en el sistema educativo como sistema escolar

Presynaptic Dopamine D2 Receptors Modulate [3H]GABA Release at StriatoPallidal Terminals via Activation of PLC ? IP3 ? Calcineurin and Inhibition of AC ? cAMP ? PKA Signaling Cascades

Documento de investigación que reporte la actividad del receptor D2, en la vía estriado-palidal.bstract—Striatal dopamine D2 receptors activate the PLC ? IP3 ? Calcineurin-signaling pathway to modulate the neural excitability of En+ Medium-sized Spiny GABAergic neurons (MSN) through the regulation of L-type Ca2+ channels. Presynaptic dopaminergic D2 receptors modulate GABA release at striatopallidal terminals through L-type Ca2+ channels as well, but their signaling pathway is still undetermined. Since D2 receptors are Gi/o-coupled and negatively modulate adenylyl cyclase (AC), we investigated whether presynaptic D2 recep- tors modulate GABA release through the same signaling cascade that controls excitability in the striatum or by the inhibition of AC and decreased PKA activity. Activation of D2 receptors stimulated formation of [3H]IP1 and decreased Forskolin-stimulated [3H]cAMP accumulation in synaptosomes from rat Globus Pallidus. D2 receptor activation with Quinpirole in the presence of L 745,870 decreased, in a dose-dependent manner, K+-induced [3H] GABA release in pallidal slices. The effect was prevented by the pharmacological blockade of Gi/o bc subunit effects with Gallein, PLC with U 73122, IP3 receptor activation with 4-APB, Calcineurin with FK506. In addition, when release was stimulated with Forskolin to activate AC, D2 receptors also decreased K+-induced [3H]GABA release, an effect occluded with the effect of the blockade of PKA with H89 or stimulation of release with the cAMP analog 8-Br-cAMP. These data indicate that D2 receptors modulate [3H]GABA release at striatopallidal terminals by activating the PLC ? IP3 ? Calcineurin-signaling cascade, the same one that modulates excitability in soma. Additionally, D2 receptors inhibit release when AC is active. Both mechanisms appear to converge to regulate the activity of presynaptic L-type Ca2+ channels. ! 2018 IBRO. Published by Elsevier Ltd. All rights reserved

Formulations of Curcumin Nanoparticles for Brain Diseases

Curcumin is a polyphenol that is obtained from Curcuma longa and used in various areas, such as food and textiles. Curcumin has important anti-inflammatory and antioxidant properties that allow it to be applied as treatment for several emerging pathologies. Remarkably, there are an elevated number of publications deriving from the terms “curcumin„ and “curcumin brain diseases„, which highlights the increasing impact of this polyphenol and the high number of study groups investigating their therapeutic actions. However, its lack of solubility in aqueous media, as well as its poor bioavailability in biological systems, represent limiting factors for its successful application. In this review article, the analysis of its chemical composition and the pivotal mechanisms for brain applications are addressed in a global manner. Furthermore, we emphasize the use of nanoparticles with curcumin and the benefits that have been reached as an example of the extensive advances in this area of health

Dopamine D4 receptor modulates inhibitory transmission in pallido- pallidal terminals and regulates motor behavior

Two major groups of terminals release GABA within the Globus pallidus; one group is constituted by projections from striatal neurons, while endings of the intranuclear collaterals form the other one. Each neurons’ population expresses different subtypes of dopamine D2- like receptors: D2R subtype is expressed by encephalin- positive MSNs, while pallidal neurons express the D4R subtype. The D2R modulates the firing rate of striatal neurons and GABA release at their projection areas, while the D4R regulates Globus pallidus neurons excitability and GABA release at their projection areas. However, it is unknown if these receptors control GABA release at pallido- pallidal collaterals and regulate motor behavior. Here, we present neurochemical evidence of protein content and binding of D4R in pallidal synaptosomes, control of [3H] GABA release in pallidal slices of rat, electrophysiological evidence of the presence of D4R on pallidal recurrent collaterals in mouse slices, and turning behavior induced by D4R antagonist microinjected in amphetamine challenged rats. As in projection areas of pallidal neurons, GABAergic transmission in pallido- pallidal recurrent synapses is under modulation of D4R, while the D2R subtype, as known, modulates striato- pallidal projections. Also, as in projection areas, D4R contributes to control the motor activity differently than D2R. This study could help to understand the organization of intra- pallidal circuitry.GABA input to the GP via striato- pallidal projections is modulated by D2R while input via recurrent intra- nuclear collaterals is modulated by D4R.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163974/1/ejn15020_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163974/2/ejn15020-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163974/3/ejn15020.pd