Cannabinoids attenuate the effects of aging upon neuroinflammation and neurogenesis.
WIN-55,212-2 (WIN-2) can elicit anti-inflammatory and cognitive-enhancing effect in aged rats. The current study was designed to determine the differential role of the endocannabinoid receptor sub-types 1 (CB1) and 2 (CB2) and transient receptor potential vanilloid 1 receptor (TRPV1) in the reduction of age-associated brain inflammation and their effects on neurogenesis in the dentate gyrus of aged rats. Our results demonstrate that 1) the antagonist actions of WIN-2 at the TRPV1 receptor are responsible for the reduction in microglial activation and 2) the agonist actions of WIN-2 at CB1/2 receptors can trigger neurogenesis in the hippocampus of aged rats. Chronic treatment with WIN-2 established an anti-inflammatory cytokine profile within the hippocampus. Our results provide insight into the role of the endocannabinoid and vanilloid systems upon two different and detrimental aspects of normal and pathological aging, chronic neuroinflammation and decline in neurogenesis.
Marchalant
Yannick
Y
Department of Psychology, The Ohio State University, Columbus, 43210, USA.
Brothers
Holly M
HM
Norman
Greg J
GJ
Karelina
Kate
K
DeVries
A Courtney
AC
Wenk
Gary L
GL
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D048588:Benzoxazines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005911:Gliosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D048588:Benzoxazines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D016207:Cytokines; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone