Cannabidiol-Enriched Extract Reduced the Cognitive Impairment but Not the Epileptic Seizures in a Lafora Disease Animal Model

Introduction: Lafora disease (LD) is a rare form of progressive infantile epilepsy in which rapid neurological deterioration occurs as the disease advances, leading the patients to a vegetative state and then death, usually within the first decade of disease onset. Based on the capacity of the endogenous cannabinoid system (ECS) to modulate several cellular processes commonly altered in many neurodegenerative processes, as well as the antiepileptic properties of certain natural cannabinoids, the aim of this study was to evaluate the role of the ECS in LD progression. Materials and Methods: We tested whether a natural cannabis extract highly enriched in cannabidiol (CBD) might be effective in curbing the pathological phenotype of malin knockout (KO) mice as an animal model of LD. Results: Our results reveal for the first time that alterations in the ECS occur during the evolution of LD, mainly at the level of CB1, CB2, and G protein-coupled receptor 55 (GPR55) receptor expression, and that a CBD-enriched extract (CBDext) is able to reduce the cognitive impairment exhibited by malin KO mice. However, in contrast to what has previously been reported for other kinds of refractory epilepsy in childhood, the CBD-enriched extract does not reduce the severity of the epileptic seizures induced in this animal model of LD. Conclusions: In summary, this study reveals that the ECS might play a role in LD and that a CBD-enriched extract partially reduces the dementia-like phenotype, but not the increased vulnerability to epileptic seizures, exhibited by an animal model of such a life-threatening disease.Fil: Aso, Ester. Universidad de Barcelona; EspañaFil: Andrés-Benito, Pol. Universidad de Barcelona; EspañaFil: Grau-Escolano, Jordi. Universidad de Barcelona; EspañaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Sanz, Pascual. Consejo Superior de Investigaciones Científicas; EspañaFil: Ferrer, Isidre. Universidad de Barcelona; Españ

NADPH oxidase and mitochondria are relevant sources of superoxide anion in the oxinflammatory response of macrophages exposed to airborne particulate matter

Exposure to ambient air particulate matter (PM) is associated with increased cardiorespiratory morbidity and mortality. In this context, alveolar macrophages exhibit proinflammatory and oxidative responses as a result of the clearance of particles, thus contributing to lung injury. However, the mechanisms linking these pathways are not completely clarified. Therefore, the oxinflammation phenomenon was studied in RAW 264.7 macrophages exposed to Residual Oil Fly Ash (ROFA), a PM surrogate rich in transition metals. While cell viability was not compromised under the experimental conditions, a proinflammatory phenotype was observed in cells incubated with ROFA 100 μg/mL, characterized by increased levels of TNF-α and NO production, together with PM uptake. This inflammatory response seems to precede alterations in redox metabolism, characterized by augmented levels of H2O2, diminished GSH/GSSG ratio, and increased SOD activity. This scenario resulted in increased oxidative damage to phospholipids. Moreover, alterations in mitochondrial respiration were observed following ROFA incubation, such as diminished coupling efficiency and spare respiratory capacity, together with augmented proton leak. These findings were accompanied by a decrease in mitochondrial membrane potential. Finally, NADPH oxidase (NOX) and mitochondria were identified as the main sources of superoxide anion ([Formula presented]) in our model. These results indicate that PM exposure induces direct activation of macrophages, leading to inflammation and increased reactive oxygen species production through NOX and mitochondria, which impairs antioxidant defense and may cause mitochondrial dysfunction

CB1 Cannabinoid Receptor is a Target for Neuroprotection in Light Induced Retinal Degeneration

In the last few years, an increasing interest in the neuroprotective effect of cannabinoidshas taken place. The aim of the present work was to study the effects of modulatingcannabinoid receptor 1 (CB1) in the context of light induced retinal degeneration (LIRD),using an animal model that resembles many characteristics of human age-related maculardegeneration (AMD) and other degenerative diseases of the outer retina. Sprague Dawleyrats (n = 28) were intravitreally injected in the right eye with either a CB1 agonist (ACEA), oran antagonist (AM251). Contralateral eyes were injected with respective vehicles ascontrols. Then, rats were subjected to continuous illumination (12,000 lux) for 24 h.Retinas from 28 animals were processed by GFAP-immunohistochemistry (IHC),TUNEL technique, Western blotting (WB), or qRT-PCR. ACEA-treated retinas showeda significantly lower number of apoptotic nuclei in the outer nuclear layer (ONL), lower levelsof activated Caspase-3 by WB, and lower levels of glial reactivity by both GFAP-IHC andWB. qRT-PCR revealed that ACEA significantly decreased the expression of Bcl-2 andCYP1A1. Conversely, AM251-treated retinas showed a higher number of apoptotic nucleiin the ONL, higher levels of activated Caspase-3 by WB, and higher levels of glial reactivityas determined by GFAP-IHC and WB. AM251 increased the expression of Bcl-2, Bad,Bax, Aryl hydrocarbon Receptor (AhR), GFAP, and TNFα. In summary, the stimulation ofthe CB1 receptor, previous to the start of the pathogenic process, improved the survival ofphotoreceptors exposed to LIRD. The modulation of CB1 activity may be used as aneuroprotective strategy in retinal degeneration and deserves further studiesFil: Soliño, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Larráyoz, Ignacio M.. Center For Biomedical Research Of La Rioja; EspañaFil: Lopez, Ester Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Rey Funes, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Bareiro, Nidia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Loidl, Cesar Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Girardi, Elena Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Martinez, Alfredo. Center For Biomedical Research Of La Rioja; EspañaFil: López, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

NADPH oxidase and mitochondria are relevant sources of superoxide anion in the oxinflammatory response of macrophages exposed to airborne particulate matter

Exposure to ambient air particulate matter (PM) is associated with increased cardiorespiratory morbidity and mortality. In this context, alveolar macrophages exhibit proinflammatory and oxidative responses as a result of the clearance of particles, thus contributing to lung injury. However, the mechanisms linking these pathways are not completely clarified. Therefore, the oxinflammation phenomenon was studied in RAW 264.7 macrophages exposed to Residual Oil Fly Ash (ROFA), a PM surrogate rich in transition metals. While cell viability was not compromised under the experimental conditions, a proinflammatory phenotype was observed in cells incubated with ROFA 100 μg/mL, characterized by increased levels of TNF-α and NO production, together with PM uptake. This inflammatory response seems to precede alterations in redox metabolism, characterized by augmented levels of H2O2, diminished GSH/GSSG ratio, and increased SOD activity. This scenario resulted in increased oxidative damage to phospholipids. Moreover, alterations in mitochondrial respiration were observed following ROFA incubation, such as diminished coupling efficiency and spare respiratory capacity, together with augmented proton leak. These findings were accompanied by a decrease in mitochondrial membrane potential. Finally, NADPH oxidase (NOX) and mitochondria were identified as the main sources of superoxide anion ([Formula presented]) in our model. These results indicate that PM exposure induces direct activation of macrophages, leading to inflammation and increased reactive oxygen species production through NOX and mitochondria, which impairs antioxidant defense and may cause mitochondrial dysfunction.Fil: Cáceres, Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Paz, Mariela Laura. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Garcés, Mariana. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Calabró López, María Valeria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Magnani, Natalia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; ArgentinaFil: Martinefski, Manuela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tasat, Deborah. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Tripodi, Valeria Paula. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valacchi, Giuseppe. Università di Ferrara; ItaliaFil: Alvarez, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Gonzalez Maglio, Daniel Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; ArgentinaFil: Evelson, Pablo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentin

Neuronal and synaptic morphological alterations in the hippocampus of cannabinoid receptor type 1 knockout mice

Cannabinoid receptor type 1 (CB1R) modulates synaptic activity and is widely distributed in brain areas such as the hippocampus, cerebellum, cerebral cortex, and striatum, among others. CB1R is involved in processes such as memory, learning, motor coordination, and mood. Genetic deletion of CB1R causes behavioral alterations. In this work, we evaluated neuronal morphology and synaptic structure in the hippocampus of adult male CB1R knockout mice (CB1R−/−). Morphological changes in the CB1R−/− hippocampus evidenced a decrease in the expression of cytoskeletal proteins neurofilaments 160 KDa, neurofilaments 200 KDa, and microtubule-associated protein 2. CA1 neurons showed decreased arborization and changes in synaptic structure such as lower thickness of postsynaptic density and a reduction in synaptophysin levels. Results obtained in the present work provide evidence of the participation of CB1R in the establishment of neuronal structure and networks that could have an important role in neuronal plasticity. In addition, these changes observed in CB1R−/− could be correlated with behavioral alterations reported.Fil: Soriano, Delia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Vacotto, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Oleanolic acid: a promising neuroprotective agent for cerebral ischemia

License Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0).Stroke is considered the most common and severely disabling neurological disease. It is one of the leading causes of death after heart disease and cancer, causing 10% deaths worldwide and involving risk factors such as smoking, obesity and nutritional disbalance. Disability affects 75% of stroke survivors through severe mental and/or physical impairment depending on the affected brain area (Go et al., 2014).This work was supported by UBACYT 20020130100258BA (A.B.), PIP CONICET 00269 (A.B.) and UBACYT 20020130300033BA (L.C.).Peer Reviewe

Further evidence for the neuroprotective role of oleanolic acid in a model of focal brain hypoxia in rats

Ischemic brain injury is a dynamic process involving oxidative stress, inflammation, cell death and the activation of endogenous adaptive and regenerative mechanisms depending on the activation of transcription factors such as hypoxia-inducible factor 1-alpha. Accordingly, we have previously described a new focal hypoxia model by direct intracerebral cobalt chloride injection. In turn, oleanolic acid, a plantderived triterpenoid, has been extensively used in Asian countries for its anti-inflammatory and antitumor properties. A variety of novel pharmacological effects have been attributed to this triterpenoid, including beneficial effects on neurodegenerative disorders - including experimental autoimmune encephalomyelitis - due to its immunomodulatory activities at systemic level, as well as within the central nervous system. In this context, we hypothesize that this triterpenoid may be capable of exerting neuroprotective effects in ischemic brain, suppressing glial activities that contribute to neurotoxicity while promoting those that support neuronal survival. In order to test this hypothesis, we used the intraperitoneal administration of oleanoic acid in adult rats for seven days previous to focal cortical hypoxia induced by cobalt chloride brain injection. We analyzed the neuroprotective effect of oleanoic acid from a morphological point of view, focusing on neuronal survival and glial reaction.This study is supported by grants UBACYT000093 (A.B.)Peer Reviewe

Further evidence of anxiety- and depression-like behavior for total genetic ablation of cannabinoid receptor type 1

Cannabinoid receptor type 1 (CB1R) is the most abundant cannabinoid receptor in central nervous system. Clinical studies and animal models have shown that the attenuation of endocannabinoid system signaling correlates with the development of psychiatric disorders such as anxiety, depression and schizophrenia. In the present work, multiple behavioral tests were performed to evaluate behaviors related to anxiety and depression in CB1R+/− and CB1R−/−. CB1R+/− mice had anxiety-related behavior similar to wild type (CB1R+/+) mice, whereas CB1R−/− mice displayed an anxious-like phenotype, which indicates that lower expression of CB1R is sufficient to maintain the neural circuits modulating anxiety. In addition, CB1R−/− mice exhibited alterations in risk assessment and less exploration, locomotion, grooming, body weight and appetite. These phenotypic characteristics observed in CB1R−/− mice could be associated with symptoms observed in human psychiatric disorders such as depression. A better knowledge of the neuromodulatory role of CB1R may contribute to understand scope and limitations of the development of medical treatments.Fil: Soriano, Delia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Endocannabinoids and Endocrine System

Son conocidas las propiedades medicinales de la planta de cannabis a nivel mundial así como los efectos de sus derivados sintéticos en la terapéutica de diferentes enfermedades. En los países donde el consumo medicinal ha sido legalizado su utilidad en el tratamiento de enfermedades del sistema nervioso central ha generado amplios beneficios en los pacientes. En las últimas décadas ha tomado relevancia su efecto paliativo del dolor crónico en pacientes con patologías oncológicas o degenerativas y sus beneficios antiproliferativos e inmunomduladores. El sistema endocannabinoide está representado por ligandos endógenos, derivados de ácidos grasos, que tienen efectos sobre receptores expresados en distintas localizaciones del organismo. En el transcurso de los años se han descripto múltiples sitios target entre ellos los órganos del sistema endócrino. A pesar de estos avances sigue siendo un desafío determinar con certeza los efectos, la titulación de la dosis terapéutica para cada individuo y la detección de ligandos sintéticos agonistas y antagonistas selectivos para los diferentes receptores. En esta revisión describiremos los aspectos generales del sistema endocannabinoide y sus efectos sobre los órganos endócrinos haciendo foco en las implicancias sobre el metabolismo de los hidratos de carbono, el tejido adiposo y la función reproductiva.The medicinal properties of the cannabis plant are known worldwide as well as the effects of its synthetic derivatives in the therapeutics of different diseases. In countries where medicinal consumption has been legalized, its usefulness in the treatment of diseases of the central nervous system has generated extensive benefits in patients. In recent decades, its palliative effect of chronic pain in patients with oncological or degenerative pathologies and its antiproliferative and immunomodulating benefits have become relevant. The endocannabinoid system is represented by endogenous ligands, derived from fatty acids, which have effects on receptors expressed in different locations of the body. Over the years, multiple target sites have been described, including the organs of the endocrine system. Despite these advances, it remains a challenge to determine with certainty the effects, the therapeutic dose for each individual and the detection of synthetic ligands agonists and selective antagonists for the different receptors. In this review we will describe the general aspects of the endocannabinoid system and its effects on endocrine organs, focusing on the implications for carbohydrate metabolism, adipose tissue and reproductive function.Fil: Belingeri, Maria Soledad. Hospital Municipal General de Agudos Doctor José Penna; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Paganelli, Alejandra Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Caltana, Laura Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Further evidence for the neuroplastic role of cannabinoids: a study in organotypic hippocampal slice cultures

Endocannabinoid receptors CB1R and CB2R are present in the CNS and modulate synaptic activity. By using an in vitro model, two concentrations of CB1R agonist ACEA at 0.5 and 5 μM doses and CB1R antagonist AM251 at 1 and 10 μM doses were administered in organotypic slice cultures of mouse hippocampus, and their effects on neurons and glial cells were analyzed at different time points. Exposure to low concentrations of ACEA (0.5 μM) did not seem to affect tissue organization, neuronal morphology, or glial response. In contrast, at a higher concentration of ACEA, many neurons in the dentate gyrus exhibited strong caspase-3 immunoreactivity. After treatment with AM251, we observed an increase in caspase-3 immunoreactivity and a downregulation of CB1R expression. Results show that long-term hippocampal slice cultures respond to both CB1R activation and inactivation by changing neuronal protein expression patterns. In the present study, we demonstrate that CB1R agonist ACEA promotes alterations in the neuronal cytoskeleton as well as changes in CB1R expression in organotypic hippocampal slice cultures, and that CB1R antagonist AM251 promotes neuronal death and astroglial reaction.Fil: Caltana, Laura Romina. University of Freiburg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Heimrich, Bernd. University of Freiburg; AlemaniaFil: Brusco, Herminia Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin