The synthetic cannabinoid HU-210 attenuates neural damage in diabetic mice and hyperglycemic pheochromocytoma PC12 cells

Yossi Dagon, Yosefa Avraham, Gabriela Link, Olga Zolotarev, Raphael Mechoulam, Elliot M. Berry*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageAmerican English
Pages (from-to)174-181
Number of pages8
JournalNeurobiology of Disease
Volume27
Issue number2
DOIs
StatePublished - Aug 2007

Bibliographical note

Funding Information:
The research was supported by the Binational Science Foundation (BSF) and “Women’s Health” initiative of the Hadassah Medical Organization. We would like to thank Dr Lia Vorobiav and the students: Mayer Saidian, Rafael Mevorah and Reut Pienik for their technical assistance.

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