title: The synthetic cannabinoid HU-210 attenuates neural damage in diabetic mice and hyperglycemic pheochromocytoma PC12 cells.
abstract: Diabetic neuropathy (DN) is a common complication of diabetes mellitus resulting in cognitive dysfunction and synaptic plasticity impairment. Hyperglycemia plays a critical role in the development and progression of DN, through a number of mechanisms including increased oxidative stress. Cannabinoids are a diverse family of compounds which can act as antioxidative agents and exhibit neuroprotective properties. We investigated the effect of the synthetic cannabinoid HU-210 on brain function of streptozotocin (STZ)-induced diabetic mice. These animals exhibit hyperglycemia, increased cerebral oxidative stress and impaired brain function. HU-210, through a receptor independent pathway, alleviates the oxidative damage and cognitive impairment without affecting glycemic control. To study the neuroprotective mechanism(s) involved, we cultured PC12 cells under hyperglycemic conditions. Hyperglycemia enhanced oxidative stress and cellular injuries were all counteracted by HU-210-in a dose dependent manner. These results suggest cannabinoids might have a therapeutic role in the management of the neurological complications of diabetes.
authors.affiliation: Department of Human Nutrition and Metabolism, Braun School of Public Health, Faculty of Medicine Hebrew University, Hadassah Medical School, Israel.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Dagon
authors.forename: Yosefa
authors.initials: Y
authors.lastname: Avraham
authors.forename: Gabriela
authors.initials: G
authors.lastname: Link
authors.forename: Olga
authors.initials: O
authors.lastname: Zolotarev
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Berry
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats
chemical_list: D018696:Neuroprotective Agents; D013759:Dronabinol; C062018:HU 211