Tomorrow's Nature magazine carries an article on head trauma that could inform parts of Alzheimer's research, as well. Esther Shohami at Hebrew University's Medical Faculty in Jerusalem, and colleagues there, report that an endogenous cannabinoid plays a role in the complex protective response prompted by a brain injury.
The compound, 2-Arachidonoyl glycerol (2-AG) occurs in the brain and the intestine but its physiology remains poorly understood. It can protect cerebral rat neurons from ischemia in vitro (Sinor AD et al.), and synthetic cannabinoids have been shown to reduce neuronal death in the hippocampus of rats after experimentally induced ischemia (Nagayama T et al.).
In this study, the researchers subjected mice to head trauma and analyzed the 2-AG response following this injury. 2-AG levels rose, peaking at 10-fold after four hours. When the researchers injected additional 2-AG, the mice developed 50 percent less edema and recovered faster. More directly relevant to Alzheimer's research, the treated mice also suffered less neuronal cell death. The researchers counted neurons in the CA3 area of the hippocampus, and report that control mice (head trauma without exogenous 2-AG) had lost about 40 percent of neurons in that brain area seven days after the trauma, whereas treated mice lost about 10 percent. (The hippocampus is among the brain areas most affected by neuronal death in AD.)
The authors write that these results are the first to record the neuroprotective effects of this cannabinoid. In previous work, the authors had shown that 2-AG suppresses the formation of reactive oxygen species and the inflammatory cytokine tumor necrosis factor-β, both of which contribute to the pathophysiology of brain injury. To the extent that oxidative damage and inflammation spur the loss of cells in AD, this research may well bear attention.—Gabrielle Strobel
Hypothesis Factory: Marijuana and AD
- Sinor AD, Irvin SM, Greenberg DA. Endocannabinoids protect cerebral cortical neurons from in vitro ischemia in rats. Neurosci Lett. 2000 Jan 14;278(3):157-60. PubMed.
- Nagayama T, Sinor AD, Simon RP, Chen J, Graham SH, Jin K, Greenberg DA. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci. 1999 Apr 15;19(8):2987-95. PubMed.
- Panikashvili D, Simeonidou C, Ben-Shabat S, Hanus L, Breuer A, Mechoulam R, Shohami E. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature. 2001 Oct 4;413(6855):527-31. PubMed.