title: Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus.
abstract: Voluntary exercise and endogenous cannabinoid activity have independently been shown to regulate hippocampal plasticity. The aim of the current study was to determine whether the endocannabinoid system is regulated by voluntary exercise and if these changes contribute to exercise-induced enhancement of cell proliferation. In Experiment 1, 8 days of free access to a running wheel increased the agonist binding site density of the cannabinoid CB(1) receptor; CB(1) receptor-mediated GTPgammaS binding; and the tissue content of the endocannabinoid anandamide in the hippocampus but not in the prefrontal cortex. In Experiment 2, the CB(1) receptor antagonist AM251 (1 mg kg(-1)) was administered daily to animals given free access to a running wheel for 8 days, after which cell proliferation in the hippocampus was examined through immunohistochemical analysis of the cell cycle protein Ki-67. Voluntary exercise increased proliferation of progenitor cells, as evidenced by the increase in the number of Ki-67 positive cells in the granule cell layer of the dentate gyrus (DG) in the hippocampus. However, this effect was abrogated by concurrent treatment with AM251, indicating that the increase in endocannabinoid signaling in the hippocampus is required for the exercise-induced increase in cell proliferation. These data demonstrate that the endocannabinoid system in the hippocampus is sensitive to environmental change and suggest that it is a mediator of experience-induced plasticity.
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, B.C., Canada. mhill@mail.rockefeller.edu
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Hill
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Titterness
authors.forename: Anna C
authors.initials: AC
authors.lastname: Morrish
authors.forename: Erica J
authors.initials: EJ
authors.lastname: Carrier
authors.forename: Tiffany T-Y
authors.initials: TT
authors.lastname: Lee
authors.forename: Joana
authors.initials: J
authors.lastname: Gil-Mohapel
authors.forename: Boris B
authors.initials: BB
authors.lastname: Gorzalka
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: Hillard
authors.forename: Brian R
authors.initials: BR
authors.lastname: Christie
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002452:Cell Count; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells
chemical_list: D063385:Cannabinoid Receptor Modulators; D043884:Receptor, Cannabinoid, CB1