Specific pathophysiological functions of JNK isoforms in the brain
| العنوان: | Specific pathophysiological functions of JNK isoforms in the brain |
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| المؤلفون: | 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 |
| المصدر: | European Journal of Neuroscience. 21:363-377 |
| بيانات النشر: | Wiley, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1460-9568 0953-816X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::186f3cd871b2785098217d5d69d23814 https://doi.org/10.1111/j.1460-9568.2005.03857.x |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....186f3cd871b2785098217d5d69d23814 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14609568 0953816X |
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