Regulation of ERK by cannabinoids in hippocampes
| العنوان: | Regulation of ERK by cannabinoids in hippocampes |
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| المؤلفون: | Derkinderen, P., Valjent, E., Toutant, M., Corvol, J.C., Enslen, H., Ledent, C., Trzaskos, J., Caboche, J., Girault, J.A. |
| المساهمون: | Transduction du Signal et Plasticite Dans Le Systeme Nerveux, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Interdisciplinaire en Biologie Humaine et Nucléaire, Université libre de Bruxelles (ULB), Research Laboratory, Bristol-Myers Squibb Company, P.D. was supported by a Poste d'accueil Institut National de la Santé et de la Recherche Médicale. This work was supported in part by grants from Mission Interministerielle de Lutte contre les Drogues et la Toxicomanie, Human Frontier Science Programme Organization, Fondation pour la Recherche Médicale, Fondation Schlumberger pour l'Enseignement et la Recherche, and Action Concertée Incitative (Biologie du Développement et Physiologie Intégrative). |
| المصدر: | Journal of Neuroscience Journal of Neuroscience, Society for Neuroscience, 2003, 23, pp.2371-2382 Journal of Neuroscience, 2003, 23, pp.2371-2382 |
| بيانات النشر: | HAL CCSD, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | c-Fos, THC, 2-AG, hippocampus, phosphorylation, Zif268, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, immediate-early genes, LPA, cannabinoids, ERK, BDNF, nervous system, CB1-R, Fyn, anandamide, lipids (amino acids, peptides, and proteins), rat, slices, mouse |
| الوصف: | Endocannabinoids form a novel class of intercellular messengers, the functions of which include retrograde signaling in the brain and mediation or modulation of several types of synaptic plasticity. Yet, the signaling mechanisms and long-term effects of the stimulation of CB1 cannabinoid receptors (CB1-R) are poorly understood. We show that anandamide, 2-arachidonoyl-glycerol, and Delta9-tetrahydrocannabinol (THC) activated extracellular signal-regulated kinase (ERK) in hippocampal slices. In living mice, THC activated ERK in hippocampal neurons and induced its accumulation in the nuclei of pyramidal cells in CA1 and CA3. Both effects were attributable to stimulation of CB1-R and activation of MAP kinase/ERK kinase (MEK). In hippocampal slices, the stimulation of ERK was independent of phosphatidyl-inositol-3-kinase but was regulated by cAMP. The endocannabinoid-induced stimulation of ERK was lost in Fyn knock-out mice, in slices and in vivo, although it was insensitive to inhibitors of Src-family tyrosine kinases in vitro, suggesting a noncatalytic role of Fyn. Finally, the effects of cannabinoids on ERK activation were dependent on the activity of glutamate NMDA receptors in vivo, but not in hippocampal slices, indicating the existence of several pathways linking CB1-R to the ERK cascade. In vivo THC induced the expression of immediate-early genes products (c-Fos protein, Zif268, and BDNF mRNAs), and this induction was prevented by an inhibitor of MEK. The strong potential of cannabinoids for inducing long-term alterations in hippocampal neurons through the activation of the ERK pathway may be important for the physiological control of synaptic plasticity and for the general effects of THC in the context of drug abuse. |
| اللغة: | English |
| تدمد: | 0270-6474 1529-2401 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::6d7b67e9ff7cd8ce3ccd9e6b2b8db8e2 https://hal.archives-ouvertes.fr/hal-00080008 |
| رقم الأكسشن: | edsair.dedup.wf.001..6d7b67e9ff7cd8ce3ccd9e6b2b8db8e2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02706474 15292401 |
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