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Immunohistochemical Description of the Endogenous Cannabinoid System in the Rat Cerebellum and Functionally Related Nuclei

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Immunohistochemical Description of the Endogenous Cannabinoid System in the Rat Cerebellum and Functionally Related Nuclei ( immunohistochemical-description-endogenous-cannabinoid-syste )

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THE JOURNAL OF COMPARATIVE NEUROLOGY 509:400–421 (2008) Immunohistochemical Description of the Endogenous Cannabinoid System in the Rat Cerebellum and Functionally Related Nuclei JUAN SUA ́ REZ,1* FRANCISCO JAVIER BERMU ́ DEZ-SILVA,1 KEN MACKIE,2 CATHERINE LEDENT,3 ANDREAS ZIMMER,4 BENJAMIN F. CRAVATT,5 AND FERNANDO RODRI ́GUEZ DE FONSECA1* 1Laboratorio de Medicina Regenerativa, Fundacio ́n IMABIS, 29010 Ma ́laga, Spain 2Departments of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47401 3Institut de Recherche Interdisciplinaire en Biologie Humaine et Mole ́culaire, Universite ́ Libre de Bruxelles, B-1050 Bruxelles, Belgium 4Institute of Molecular Psychiatry, University of Bonn, 53115 Bonn, Germany 5Chemical Biology and Cell Biology, The Scripps Research Institute, La Jolla, California 92037 ABSTRACT We report a detailed analysis of the distribution of relevant proteins of the endogenous cannabinoid system in the rat cerebellum (cerebellar cortex and deep cerebellar nuclei) and the two functionally related nuclei, the vestibular nuclei and the inferior olive. These proteins include the two main cannabinoid receptors (CB1 and CB2), the enzymes involved in canna- binoid biosynthesis (DAGL’, DAGL’, and NAPE-PLD), and the endocannabinoid- degradating enzymes (FAAH and MAGL). With regard to the cerebellar cortex, these data confirm several published reports on the distribution of cannabinoid CB1 receptors, DAGL’, MAGL, and FAAH, which suggests a role of endocannabinoids as retrograde messengers in the synapses of the Purkinje cells by either parallel fibers of granule cells or climbing fibers from the inferior olive or GABAergic interneuron. Additionally, we describe the presence of CB2 receptors in fibers related to Purkinje somata (Pinceau formations) and dendrites (parallel fibers), suggesting a potential role of this receptor in the retrograde cannabinoid signaling. A remarkable finding of the present study is the description of the different elements of the endogenous cannabinoid system in both the main afferent nuclei to the cerebellar cortex (the inferior olive) and the efferent cerebellar pathway (the deep cerebellar nuclei). The presence of the endogenous cannabinoid system at this level establishes the basis for endocannabinoid-mediated synaptic plasticity as a control mechanism in motor learning, opening new research lines for the study of the contribution of this system in gait disorders affecting the cerebellum. J. Comp. Neurol. 509:400–421, 2008. © 2008 Wiley-Liss, Inc. Indexing terms: endocannabinoid system; cerebellar cortex; deep cerebellar nuclei; vestibular nuclei; inferior olive; CB1 receptor; CB2 receptor; immunohistochemistry This article includes Supplementary Material available via the Internet at http://www.interscience.wiley.com/jpages/0021-9967/suppmat. Grant sponsor: Consejer ́ıa de Salud (Junta de Andaluc ́ıa); Grant num- ber: PI-0220; MEC; Grant number: SAF 2004/07762; Grant sponsor: Insti- tuto de Salud Carlos III; Grant number: 07/1226; Grant number: 07/0880; Grant sponsor: Plan Nacional Sobre Drogas; Grant sponsor: Consejeria de Innovacio ́n Ciencia y Empresa (Junta de Andaluc ́ıa); Grant number: RE- DES RTA RD06/001; Grant sponsor: 5th Framework Programme; Grant number: TARGALC QLRT-2001-01048. *Correspondence to: Juan Sua ́rez and Fernando Rodr ́ıguez de Fonseca, Laboratorio de Medicina Regenerativa, Fundacio ́n IMABIS, Avenida Carlos Haya 82, 29010 Ma ́laga, Spain. E-mail: juan.suarez@fundacionimabis.org; fernando.rodriguez@fundacionimabis.org Received 21 February 2007; Revised 14 August 2007; Accepted 28 April 2008 DOI 10.1002/cne.21774 Published online in Wiley InterScience (www.interscience.wiley.com). © 2008 WILEY-LISS, INC.

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