title: Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.
abstract: Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.
authors: UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III Madrid, Spain.
authors: Patricia
authors: P
authors: Rivera
authors: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg-University of Mainz Mainz, Germany.
authors: Laura
authors: L
authors: Bindila
authors: Institut Hospital del Mar d'Investigacions Mediques Barcelona, Spain ; Facultat de Medicina, Universitat Autonoma de Barcelona Barcelona, Spain.
authors: Antoni
authors: A
authors: Pastor
authors: Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga Málaga, Spain.
authors: Margarita
authors: M
authors: Pérez-Martín
authors: UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III Madrid, Spain.
authors: Francisco J
authors: FJ
authors: Pavón
authors: UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III Madrid, Spain.
authors: Antonia
authors: A
authors: Serrano
authors: CIBER OBN, Instituto de Salud Carlos III Madrid, Spain ; Institut Hospital del Mar d'Investigacions Mediques Barcelona, Spain ; Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF) Barcelona, Spain.
authors: Rafael
authors: R
authors: de la Torre
authors: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg-University of Mainz Mainz, Germany.
authors: Beat
authors: B
authors: Lutz
authors: UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III Madrid, Spain.
authors: Fernando
authors: F
authors: Rodríguez de Fonseca
authors: UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga Málaga, Spain ; CIBER OBN, Instituto de Salud Carlos III Madrid, Spain.
authors: Juan
authors: J
authors: Suárez
keywords: FAAH; URB597; cannabinoids; energy metabolism; gliosis; neurogenesis