Endocannabinoid 2-arachidonylglycerol protects primary cultured neurons against homocysteine-induced impairments in rat caudate nucleus through CB1 receptor.

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.