GABAergic and Cortical and Subcortical Glutamatergic Axon Terminals Contain CB1 Cannabinoid Receptors in the Ventromedial Nucleus of the Hypothalamus

Background: Type-1 cannabinoid receptors (CB1R) are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that participates in homeostatic and behavioral functions including food intake. Although CB1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. Methodology/Principal Findings: Light and electron microscopy techniques were used to analyze CB1R distribution in the VMH of CB1R-WT, CB1R-KO and conditional mutant mice bearing a selective deletion of CB1R in cortical glutamatergic (Glu-CB1R-KO) or GABAergic neurons (GABA-CB1R-KO). At light microscopy, CB1R immunolabeling was observed in the VMH of CB1R-WT and Glu-CB1R-KO animals, being remarkably reduced in GABA-CB1R-KO mice. In the electron microscope, CB1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB1R immunopositive profiles and CB1R density in terminals making asymmetric or symmetric synapses in CB1R-WT mice. Furthermore, the proportion of CB1R immunopositive terminals/preterminals in CB1R-WT and Glu-CB1R-KO mice was reduced in GABA-CB1R-KO mutants. CB1R density was similar in all animal conditions. Finally, the percentage of CB1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB1R-KO mutants relative to CB1R-WT mice, indicating that CB1R was distributed in cortical and subcortical excitatory synaptic terminals. Conclusions/Significance: Our anatomical results support the idea that the VMH is a relevant hub candidate in the endocannabinoid-mediated modulation of the excitatory and inhibitory neurotransmission of cortical and subcortical pathways regulating essential hypothalamic functions for the individual's survival such as the feeding behavior.

SU-8 microprobes for biomedical applications

152 p. : il.

Arquitectura subcelular del sistema endocannabinoide en el núcleo ventromedial del hipotálamo de ratón

356 p. : il., graf. Nota: Contiene versión resumida en inglés p.237-256 con el título “Subcellular architecture of the endocannabinoid system in the mouse ventromedial nucleus of the hypothalamus”

GABA release by hippocampal astrocytes

10 p.

Visualization by High Resolution Immunoelectron Microscopy of the Transient Receptor Potential Vanilloid-1 at Inhibitory Synapses of the Mouse Dentate Gyrus

We have recently shown that the transient receptor potential vanilloid type 1 (TRPV1), a non-selective cation channel in the peripheral and central nervous system, is localized at postsynaptic sites of the excitatory perforant path synapses in the hippocampal dentate molecular layer (ML). In the present work, we have studied the distribution of TRPV1 at inhibitory synapses in the ML. With this aim, a preembedding immunogold method for high resolution electron microscopy was applied to mouse hippocampus. About 30% of the inhibitory synapses in the ML are TRPV1 immunopositive, which is mostly localized perisynaptically (similar to 60% of total immunoparticles) at postsynaptic dendritic membranes receiving symmetric synapses in the inner 1/3 of the layer. This TRPV1 pattern distribution is not observed in the ML of TRPV1 knock-out mice. These findings extend the knowledge of the subcellular localization of TRPV1 to inhibitory synapses of the dentate molecular layer where the channel, in addition to excitatory synapses, is present.

Localización por imagen de alta resolución del sistema cannabinoide endógeno en la mitocondria del músculo estriado de roedor

96 p.

Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle

Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of alpha-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle-regulated by both diet and CB1 receptor activity-through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD.

La modernización urbana de Mondragón hacia 1900: la contribución de Pedro de Viteri

[ES] Pedro de Viteri (Mondragón, 1833-Biarritz, 1908) llegó a su villa natal en 1893, después de haber vivido en Francia desde que era un niño. Volvió con el ánimo de emprender una labor filantrópica que cambió la fisonomía urbana de Mondragón, imprimiendo un aire nuevo y moderno a una villa que a la sazón distaba mucho del ambiente en el que él se había movido.

Aportaciones a la escultura romanista en Gipuzkoa. Pedro de Goicoechea y el retablo mayor de San Miguel de Irura

[ES] En la iglesia de San Miguel Arcángel, en Irura, encontramos uno de los retablos más interesantes de finales del Renacimiento en Gipuzkoa. El altar posee relieves y tallas de estilo romanista de gran calidad, junto con una mazonería manierista. La obra fue realizada en las postrimerías del siglo XVI por los artistas Pedro de Goicoechea y Jerónimo de Larrea, miembros del taller de Tolosa, siguiendo las trazas dadas por escultor Juan de Goicoechea.

San Pedro berraktibatzen

Pasai San Pedroko Herrikoplaza-ko inguruaren birplanteaketa erabilera berrien integrazioaren eta irisgarritasunaren hobekuntzaren bidez.

El tope salarial en la Liga de Fútbol Profesional Española: el caso de Pedro León

El Pasado 21 de mayo del 2014 la Asamblea de la Liga de Fútbol Profesional aprobó el reglamento de Control Económico de los Clubes y Sociedades Anónimas Deportivas. Tres meses después la LFP publico que el Getafe no podía inscribir al jugador Pedro León Sánchez-Gil por incumplimiento de los reglamentos ya citados. La presente revisión bibliográfica tiene como objetivos clarificar las diferentes normativas que se presentan por parte la de LFP y RFEF. Además de exponer los diferentes procedimientos que se han seguido por parte de Pedro Sánchez León, Getafe, AFE, CSD, LFP y RFEF en relación a la prohibición de la participación del nombrado jugador en la Liga.

2015 urteko Trintxerpe-San Pedro San Silvestre lasterketarako proiektua

2015. urteko Trintxerpe-San Pedro San Silvestre lasterketaren proiektua izango da lan hau. Lasterketa osoa antolatuko da.