Publication Date:
2003-10-04
Description:
Abnormally high spiking activity can damage neurons. Signaling systems to protect neurons from the consequences of abnormal discharge activity have been postulated. We generated conditional mutant mice that lack expression of the cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent inhibitory interneurons. In mutant mice,the excitotoxin kainic acid (KA) induced excessive seizures in vivo. The threshold to KA-induced neuronal excitation in vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA administration rapidly raised hippocampal levels of anandamide and induced protective mechanisms in wild-type principal hippocampal neurons. These protective mechanisms could not be triggered in mutant mice. The endogenous cannabinoid system thus provides on-demand protection against acute excitotoxicity in central nervous system neurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marsicano, Giovanni -- Goodenough, Sharon -- Monory, Krisztina -- Hermann, Heike -- Eder, Matthias -- Cannich, Astrid -- Azad, Shahnaz C -- Cascio, Maria Grazia -- Gutierrez, Silvia Ortega -- van der Stelt, Mario -- Lopez-Rodriguez, Maria Luz -- Casanova, Emilio -- Schutz, Gunther -- Zieglgansberger, Walter -- Di Marzo, Vincenzo -- Behl, Christian -- Lutz, Beat -- New York, N.Y. -- Science. 2003 Oct 3;302(5642):84-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Genetics of Behaviour, Max-Planck-Institute of Psychiatry, Kraepelinstrabetae 2-10, 80804 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14526074" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Arachidonic Acids/*metabolism/pharmacology
;
Brain/drug effects/*metabolism
;
Brain-Derived Neurotrophic Factor/genetics/metabolism
;
Cannabinoids/*metabolism
;
Endocannabinoids
;
Epilepsy/*metabolism/physiopathology
;
Excitatory Amino Acid Agonists/pharmacology
;
Excitatory Postsynaptic Potentials
;
Furans/pharmacology
;
Gene Expression Regulation/drug effects
;
Genes, Immediate-Early
;
Glutamic Acid/metabolism
;
Glycerides/metabolism
;
Hippocampus/drug effects/metabolism
;
In Vitro Techniques
;
Kainic Acid/pharmacology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Mice, Knockout
;
Mice, Transgenic
;
Mitogen-Activated Protein Kinases/metabolism
;
Mutation
;
Neurons/drug effects/*metabolism/physiology
;
Neuroprotective Agents/metabolism
;
Piperidines/pharmacology
;
Polyunsaturated Alkamides
;
Prosencephalon/drug effects/metabolism
;
Pyrazoles/pharmacology
;
Receptors, Cannabinoid
;
Receptors, Drug/antagonists & inhibitors/genetics/*metabolism
;
Signal Transduction
;
gamma-Aminobutyric Acid/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
