Browsing by MeSH term "Dentate Gyrus"
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Publication BMP and WNT signalling cooperate through LEF1 in the neuronal specification of adult hippocampal neural stem and progenitor cells(Nature Publishing Group, 2018) Armenteros, Tomás; Andreu, Zoraida; Hortigüela, Rafael; Lie, D Chichung; Mira, Helena; Ministerio de Economía y Competitividad (España)Neuronal production from neural stem cells persists during adulthood in the subgranular zone of the hippocampal dentate gyrus. Extracellular signals provided by the hippocampal microenvironment regulate the neuronal fate commitment of the stem cell progeny. To date, the identity of those signals and their crosstalk has been only partially resolved. Here we show that adult rat hippocampal neural stem and progenitor cells (AH-NSPCs) express receptors for bone morphogenetic proteins (BMPs) and that the BMP/P-Smad pathway is active in AH-NSPCs undergoing differentiation towards the neuronal lineage. In vitro, exposure to the BMP2 and BMP4 ligands is sufficient to increase neurogenesis from AH-NSPCs in a WNT dependent manner while decreasing oligodendrogenesis. Moreover, BMP2/4 and WNT3A, a key regulator of adult hippocampal neurogenesis, cooperate to further enhance neuronal production. Our data point to a mechanistic convergence of the BMP and WNT pathways at the level of the T-cell factor/lymphoid enhancer factor gene Lef1. Altogether, we provide evidence that BMP signalling is an important regulator for the neuronal fate specification of AH-NSPCs cultures and we show that it significantly cooperates with the previously described master regulator of adult hippocampal neurogenesis, the WNT signalling pathway.Publication Localization of the cannabinoid CB1 receptor and the 2-AG synthesizing (DAGLα) and degrading (MAGL, FAAH) enzymes in cells expressing the Ca(2+)-binding proteins calbindin, calretinin, and parvalbumin in the adult rat hippocampus.(Frontiers Media, 2014-06-27) Rivera, Patricia; Arrabal, Sergio; Cifuentes, Manuel; Grondona, Jesús M; Pérez-Martín, Margarita; Rubio, Leticia; Vargas, Antonio; Serrano, Antonia; Pavón, Francisco-Javier; Suárez, Juan; Rodríguez de Fonseca, Fernando; [Rivera,P; Arrabal,S; Vargas,A; Serrano,A; Pavón,FJ; Suárez,J; Rodriguez de Fonseca,F] Laboratorio de Investigación, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Regional Universitario de Málaga (UGC Salud Mental), Málaga, Spain. [Rivera,P; Arrabal,S; Serrano,A; Pavón,FJ; Suárez,J; Rodriguez de Fonseca,F] CIBER OBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain. [Cifuentes,M; Grondona,JM; Pérez-Martín,M] Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, Málaga, Spain. [Cifuentes,M] CIBER BBN, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Madrid, Spain. [Rubio,L] Departamento de Anatomía y Medicina Legal, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.The retrograde suppression of the synaptic transmission by the endocannabinoid sn-2-arachidonoylglycerol (2-AG) is mediated by the cannabinoid CB1 receptors and requires the elevation of intracellular Ca(2+) and the activation of specific 2-AG synthesizing (i.e., DAGLα) enzymes. However, the anatomical organization of the neuronal substrates that express 2-AG/CB1 signaling system-related molecules associated with selective Ca(2+)-binding proteins (CaBPs) is still unknown. For this purpose, we used double-label immunofluorescence and confocal laser scanning microscopy for the characterization of the expression of the 2-AG/CB1 signaling system (CB1 receptor, DAGLα, MAGL, and FAAH) and the CaBPs calbindin D28k, calretinin, and parvalbumin in the rat hippocampus. CB1, DAGLα, and MAGL labeling was mainly localized in fibers and neuropil, which were differentially organized depending on the hippocampal CaBPs-expressing cells. CB(+) 1 fiber terminals localized in all hippocampal principal cell layers were tightly attached to calbindin(+) cells (granular and pyramidal neurons), and calretinin(+) and parvalbumin(+) interneurons. DAGLα neuropil labeling was selectively found surrounding calbindin(+) principal cells in the dentate gyrus and CA1, and in the calretinin(+) and parvalbumin(+) interneurons in the pyramidal cell layers of the CA1/3 fields. MAGL(+) terminals were only observed around CA1 calbindin(+) pyramidal cells, CA1/3 calretinin(+) interneurons and CA3 parvalbumin(+) interneurons localized in the pyramidal cell layers. Interestingly, calbindin(+) pyramidal cells expressed FAAH specifically in the CA1 field. The identification of anatomically related-neuronal substrates that expressed 2-AG/CB1 signaling system and selective CaBPs should be considered when analyzing the cannabinoid signaling associated with hippocampal functions.Publication Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.(Frontiers Media, 2015-09-29) Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco-Javier; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan; [Rivera,P; Blanco,E; Alen,F; Vargas,A; Pavón,FJ; Serrano,A; Rodríguez de Fonseca,F; Suárez,J[ UGC Salud Mental, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga-Hospital Universitario Regional de Málaga, Málaga, Spain. [Blanco,E] Departament de Pedagogia i Psicologia, Facultat de Ciències de l'Educació, Universitat de Lleida, Lleida, Spain. [Bindila,L; Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany. [Rubio,L] Departamento de Anatomía y Medicina Legal, Universidad de Málaga, Málaga, Spain.Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.