title: Endocannabinoid 2-arachidonylglycerol protects primary cultured neurons against homocysteine-induced impairments in rat caudate nucleus through CB1 receptor.
abstract: Homocysteine (Hcy) is a high risk factor for Alzheimer's disease (AD). Caudate nucleus (CN), the major component of basal ganglia in the brain, is also involved in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the true natural ligand for cannabinoid type-1 (CB1) receptors and the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from proinflammatory stimuli in the hippocampus and CN. However, it is still not well understood whether that 2-AG is also able to protect CN neurons from Hcy harmful insults. In the present work, we explored that 2-AG significantly protects CN neurons in culture against Hcy-induced response. 2-AG is capable of inhibiting elevation of Hcy-induced cyclooxygenase-2 expression associated with nuclear factor-kappaB/p38MAPK/ERK1/2 signaling pathway through CB1 receptors-dependent way in primary cultured CN neurons. Our study reveals the therapeutic potential for 2-AG for the treatment of neurodegenerative diseases, such as AD.
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei, People's Republic of China.
authors.forename: Manman
authors.initials: M
authors.lastname: Dong
authors.forename: Yongli
authors.initials: Y
authors.lastname: Lu
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Zha
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006710:Homocysteine / Q000633:toxicity; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D043884:Receptor, Cannabinoid, CB1; D006710:Homocysteine; C094503:glyceryl 2-arachidonate; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat