Specific pathophysiological functions of JNK isoforms in the brain

Autor: Mario Goetz, Axel Behrens, Elisabetha Vaudano, Malte Claussen, Damien Pearse, Chia-Yi Kuan, Erwin F. Wagner, Thomas Nicolaus, Richard A. Flavell, Rainer Kirchhof, Stephan Brecht, Jan Wessig, Gennadij Raivich, Thomas Herdegen, Vicki Waetzig, Ansgar M. Chromik, Roger J. Davis, Mette Georgi Willesen
Rok vydání: 2005
Předmět:
Male
Time Factors
Proto-Oncogene Proteins c-jun
medicine.medical_treatment
Excitotoxicity
Cell Count
medicine.disease_cause
Functional Laterality
Mice
chemistry.chemical_compound
Autonomic Denervation
Serine
Phosphorylation
Mice
Knockout
Neurons
Kainic Acid
Behavior
Animal
Cell Death
General Neuroscience
Brain
Infarction
Middle Cerebral Artery
Immunohistochemistry
Isoenzymes
Female
Facial Nerve Diseases
Axotomy
Oxidopamine
medicine.medical_specialty
Kainic acid
Tyrosine 3-Monooxygenase
Blotting
Western
Substantia nigra
Motor Activity
Biology
Neuroprotection
Internal medicine
In Situ Nick-End Labeling
medicine
Animals
Staining and Labeling
Pars compacta
Medial Forebrain Bundle
Neurotoxicity
medicine.disease
Enzyme Activation
Mice
Inbred C57BL
Endocrinology
Gene Expression Regulation
nervous system
chemistry
Brain Injuries
Neuroscience
Zdroj: European Journal of Neuroscience. 21:363-377
ISSN: 1460-9568
0953-816X
DOI: 10.1111/j.1460-9568.2005.03857.x
Popis: We have investigated the effect of JNK1 ko, JNK2 ko, JNK3 ko, JNK2+3 ko and c-JunAA mutation on neuronal survival in adult transgenic mice following ischemia, 6-hydroxydopamine induced neurotoxicity, axon transection and kainic acid induced excitotoxicity. Deletion of JNK isoforms indicated the compartment-specific expression of JNK isoforms with 46-kDa JNK1 as the main phosphorylated JNK isoform. Permanent occlusion of the MCA significantly enlarged the infarct area in JNK1 ko, which showed an increased expression of JNK3 in the penumbra. Survival of dopaminergic neurons in the substantia nigra compacta (SNC) following intrastriatal injection of 6-hydroxydopamine was transiently improved in JNK3 ko and c-JunAA mice after 7 days, but not 60 days. Following transection of the medial forebrain bundle, however, JNK3 ko conferred persisting neuroprotection of axotomised SNC neurons. None of the JNK ko and c-JunAA mutation affected the survival of facial motoneurons following peripheral axotomy when investigated after 90 days. Finally, we determined the impact of JNK ko on the survival of animals and the degeneration of hippocampal neurons following kainic acid. JNK3 ko mice were substantially resistant against and survived kainic acid-induced seizures. JNK3 ko and JNK1 ko showed a nonsignificant tendency for decreased or increased death of hippocampal neurons, respectively. Surprisingly, the deletion of a single JNK isoform did not attenuate the immunocytochemical signal of phosphorylated c-Jun irrespective on the experimental set-up. This comprehensive study provides novel insights into the context-dependent physiological and pathological functions of JNK isoforms.
Databáze: OpenAIRE
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