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dc.contributor.authorZoppi, Silvia-
dc.contributor.authorPérez-Nievas, Beatriz G.-
dc.contributor.authorMuñoz Madrigal, José Luis-
dc.contributor.authorManzanares, Jorge-
dc.contributor.authorLeza, Juan C.-
dc.contributor.authorGarcía-Bueno, Borja-
dc.date.accessioned2012-08-27T11:50:51Z-
dc.date.available2012-08-27T11:50:51Z-
dc.date.issued2011-03-
dc.identifier.citationNeuropsychopharmacology 36(4): 805-818 (2011)es_ES
dc.identifier.issn0893-133X-
dc.identifier.urihttp://hdl.handle.net/10261/55078-
dc.description14 p., 9 figures and references.es_ES
dc.description.abstractExposure to stress elicits excitoxicity and neuroinflammation in the brain, contributing to cell death and damage in stress-related neurological and neuropsychiatric diseases. The endocannabinoid system is present in stress-responsive neural circuits and has been proposed as an endogenous neuroprotective system activated in some neuropathological scenarios to restore homeostasis. To elucidate the possible regulatory role of cannabinoid receptor 1 (CB1) in stress-induced excitotoxicity and neuroinflammation, both genetic and pharmacological approaches were used alternatively: (1) wild-type (WT) and CB1 knockout mice (CB1-KO) were exposed to immobilization/acoustic stress (2 h/day for 4 days) and (2) to specifically activate CB1, the selective CB1 agonist Arachidonyl-2′-chloroethylamide (ACEA) (2.5 mg/kg) was intraperitoneally administered daily to some groups of animals. Stress exposure increased CB1 mRNA and protein expression in the prefrontal cortex of WT mice in a mechanism related to N-methyl-D-aspartate glutamate receptor activation. Daily ACEA pretreatment prevented stress-induced: (1) upregulation of CB1 mRNA and protein, (2) decrease in glutamate uptake and glutamate astroglial transporter excitatory amino acid transporter 2 expression, (3) increase in consecutive proinflammatory molecules, such as cytokines (tumor necrosis factor-α and MCP-1), nuclear factor kappa B, and enzymatic sources, such as inducible nitric oxide synthase (NOS-2) and cyclooxygenase-2 (COX-2), (4) increase in lipid peroxidation; although having no effect on plasma corticosterone. Interestingly, a possible related mechanism could be the positive ACEA modulation of the antiinflammatory pathway deoxyprostaglandin/peroxisome proliferator-activated receptor γ (15d-PGJ 2 /PPARγ). Conversely, KO animal experiments indicated that a lack of CB1 produces hypothalamic/pituitary/adrenal (HPA) axis dysregulation and exacerbates stress-induced excitotoxic/neuroinflammatory responses. These multifaceted neuroprotective effects suggest that CB1 activation could be a new therapeutic strategy against neurological/ neuropsychiatric pathologies with HPA axis dysregulation and an excitotoxic/neuroinflammatory component in their pathophysiology.es_ES
dc.description.sponsorshipThis research was supported by the Regional Government of Madrid (S-SAL/0261/2006), the Spanish Ministeries of Science and Innovation (SAF07-63138 and CIBERSAM), and Universidad Complutense-Santander (2878-920140). The research was also funded by Red Temática de Investigación Cooperativa en Salud (RETICS, Instituto de Salud Carlos III, MICINN/FEDER): Red de Trastornos Adictivos, RD06/0001/1004 (JM).es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.rightsclosedAccesses_ES
dc.subjectStresses_ES
dc.subjectExcitotoxicityes_ES
dc.subjectNeuroinflammationes_ES
dc.subjectCB1es_ES
dc.subjectPPARγes_ES
dc.titleRegulatory role of cannabinoid receptor 1 in stress-induced excitotoxicity and neuroinflammationes_ES
dc.typeartículoes_ES
dc.identifier.doi10.1038/npp.2010.214-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1038/npp.2010.214es_ES
dc.identifier.e-issn1740-634X-
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