BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice

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• dc.contributor.author Aso Pérez, Esterca
• dc.contributor.author Valverde Granados, Olgaca
• dc.contributor.author Ozaita Mintegui, Andrés, 1969-ca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Pazos, Ángelca
• dc.contributor.author Ledent, Catherineca
• dc.contributor.author Valdizán, Elsa M.ca
• dc.date.accessioned 2011-07-27T08:27:46Z
• dc.date.available 2011-07-27T08:27:46Z
• dc.date.issued 2008ca
• dc.description.abstract Stress can cause damage and atrophy of neurons in the hippocampus by deregulating the expression of neurotrophic factors that promote neuronal plasticity. The endocannabinoid system represents a physiological substrate involved in neuroprotection at both cellular and emotional levels. The lack of CB1 receptor alters neuronal plasticity and originates an anxiety-like phenotype in mice. In the present study, CB1 knockout mice exhibited an augmented response to stress revealed by the increased despair behavior and corticosterone levels showed in the tail suspension test and decreased brain derived neurotrophic factor (BDNF) levels in the hippocampus. Interestingly, local administration of BDNF in the hippocampus reversed the increased despair behavior of CB1 knockout mice, confirming the crucial role played by BDNF on the emotional impairment of these mutants. The neurotrophic deficiency seems to be specific for BDNF since no differences were found in the levels of NGF and NT-3, two additional neurotrophic factors. Moreover, BDNF impairment is not related to the activity of its specific receptor TrkB or the activity of the transcription factor CREB. These results suggest that the lack of CB1 receptor originates an enhanced response to stress and neuronal plasticity by decreasing BDNF levels in the hippocampus that lead to impairment in the responses to emotional disturbances.
• dc.description.sponsorship This study has been supported by grants from Sixth Framework Programme (NEWMOOD, LSHM-CT-2004-503474 to RM; CANSIGWITH, MIRG-6-CT-2005-014856 to AO), Ministry of Education & Science (SAF 2004/00568, SAF 2007/60249 to OV, SAF 2004/00941 to AP, BES-2005-8265 fellowship to EA) and Fundación Marqués de Valdecilla to AP.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Aso E, Ozaita A, Valdizán EM, Ledent C, Pazos Á, Maldonado R. et al. BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice. J Neurochem. 2008;105:565-72. DOI: 10.1111/j.1471-4159.2007.05149.x
• dc.identifier.doi http://dx.doi.org/10.1111/j.1471-4159.2007.05149.x
• dc.identifier.issn 0022-3042
• dc.identifier.uri http://hdl.handle.net/10230/12419
• dc.language.iso engca
• dc.publisher Wiley-Blackwellca
• dc.relation.ispartof Journal of Neurochemistry. 2008;105(2):565-72
• dc.rights © 2007 Ester Aso et al. Journal Compilation © 2007 International Society for Neurochemistry
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword CB1 cannabinoid receptor
• dc.subject.keyword Corticosterone
• dc.subject.keyword BDNF
• dc.subject.keyword CREB
• dc.subject.keyword TrkB
• dc.subject.keyword Stress
• dc.subject.other Estrès
• dc.subject.other Cannabinoides -- Receptors
• dc.title BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout miceca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/submittedVersion