6533b829fe1ef96bd1289b47
RESEARCH PRODUCT
CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity
Günther SchützShahnaz Christina AzadChristian BehlBeat LutzEmilio CasanovaMario Van Der SteltAstrid CannichMaria Grazia CascioSilvia Ortega GutierrezKrisztina MonoryWalter ZieglgänsbergerGiovanni MarsicanoVincenzo Di MarzoMaría L. López-rodríguezHeike HermannMatthias EderSharon GoodenoughSharon Goodenoughsubject
MaleCannabinoid receptorReceptors Drugmedicine.medical_treatment2-ArachidonoylglycerolExcitotoxicityHippocampal formationmedicine.disease_causeHippocampusMicechemistry.chemical_compoundPiperidinesCannabinoid receptor type 1Excitatory Amino Acid AgonistsReceptors Cannabinoidgamma-Aminobutyric AcidMice KnockoutNeuronsKainic AcidMultidisciplinaryBrainEndocannabinoid systemNeuroprotective AgentsMitogen-Activated Protein KinasesRimonabantSignal Transductionmedicine.medical_specialtyKainic acidPolyunsaturated AlkamidesGlutamic AcidMice TransgenicArachidonic AcidsIn Vitro TechniquesBiologyGlyceridesProsencephalonInternal medicinemedicineAnimalsFuransGenes Immediate-EarlyEpilepsyCannabinoidsBrain-Derived Neurotrophic FactorExcitatory Postsynaptic PotentialsMice Inbred C57BLEndocrinologyGene Expression Regulationnervous systemchemistryMutationPyrazolesCannabinoidNeuroscienceEndocannabinoidsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-10-04 | Science |