Faculty Collaboration Database

Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus 2010 Apr;20(4):513-23

Date

06/03/2009

Pubmed ID

19489006

Pubmed Central ID

PMC2847038

DOI

10.1002/hipo.20647

Scopus ID

2-s2.0-77950113882 (requires institutional sign-in at Scopus site)   108 Citations

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.

Author List

Hill MN, Titterness AK, Morrish AC, Carrier EJ, Lee TT, Gil-Mohapel J, Gorzalka BB, Hillard CJ, Christie BR

Author

Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analysis of Variance
Animals
Cannabinoid Receptor Modulators
Cell Count
Cell Cycle
Cell Proliferation
Hippocampus
Immunohistochemistry
Neurogenesis
Neurons
Physical Conditioning, Animal
Prefrontal Cortex
Radioligand Assay
Rats
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Signal Transduction
Stem Cells