NEUROSCIENCE Protective Endocannabinoids

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]

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In Science Magazine

PERSPECTIVES
NEUROSCIENCE:
Stout Guards of the Central Nervous System

R. Mechoulam and A. H. Lichtman (3 October 2003)
Science 302 (5642), 65. [DOI: 10.1126/science.1091256]
 |  Summary »  |  Full Text »  |  PDF »

RESEARCH ARTICLES
CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity

Giovanni Marsicano, Sharon Goodenough, Krisztina Monory, Heike Hermann, Matthias Eder, Astrid Cannich, Shahnaz C. Azad, Maria Grazia Cascio, Silvia Ortega Gutiérrez, Mario van der Stelt, Maria Luz López-Rodríguez, Emilio Casanova, Günther Schütz, Walter Zieglgänsberger, Vincenzo Di Marzo, Christian Behl, and Beat Lutz (3 October 2003)
Science 302 (5642), 84. [DOI: 10.1126/science.1088208]
 |  Abstract »  |  Full Text »  |  PDF »  |  Supporting Online Material »