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

Patricia Rivera, Laura Bindila, Antoni Pastor, Margarita Pérez-Martín, Francisco J. Pavón, Antonia Serrano, Rafael de la Torre, Beat Lutz, Fernando Rodríguez de Fonseca, Juan Suárez

    Research output: Contribution to journalArticleResearchpeer-review

    31 Citations (Scopus)

    Abstract

    © 2015 Rivera, Bindila, Pastor, Pérez-Martín, Pavón, Serrano, de la Torre, Lutz, Rodríguez de Fonseca and Suárez. 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 neura 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.
    Original languageEnglish
    Article number98
    JournalFrontiers in Cellular Neuroscience
    Volume9
    DOIs
    Publication statusPublished - 27 Mar 2015

    Keywords

    • Cannabinoids
    • Energy metabolism
    • FAAH
    • Gliosis
    • Neurogenesis
    • URB597

    Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this