Editors' ChoiceNeuroscience

Protective Endocannabinoids

STKE  07 Oct 2003:
Vol. 2003, Issue 203, pp. tw391-TW391
DOI: 10.1126/stke.2003.203.tw391

Neurons need to protect themselves against the risk of excessive activity that can lead to neurotoxicity. Protective mechanisms likely exist to provide on-demand defense in the case of unusually high neuronal spiking activity. Marsicano et al. (see the Perspective by Mechoulam and Lichtman) created conditional mouse mutants missing the cannabinoid receptor type 1 (CB1) in pyramidal cells but not in interneurons of the forebrain. Protection against seizures induced by the excitotoxin kainic acid was exerted via CB1 receptors in glutamatergic but not in GABAergic neurons. The seizures enhanced production of anandamide--an endogenous cannabinoid--in wild-type but not in mutant mice. Thus, the activation of the endogenous cannabinoid system is an on-demand, early, and necessary step for physiological protection against excitotoxicity.

G. Marsicano, S. Goodenough, K. Monory, H. Hermann, M. Eder, A. Cannich, S. C. Azad, M. G. Cascio, S. O. Gutiérrez, M. van der Stelt, M. L. López-Rodríguez, E. Casanova, G. Schütz, W. Zieglgänsberger, V. Di Marzo, C. Behl, B. Lutz, CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302, 84-88 (2003). [Abstract] [Full Text]

R. Mechoulam, A. H. Lichtman, Stout guards of the central nervous system. Science 302, 65-67 (2003). [Summary] [Full Text]