Activation of apoptotic pathways at muscle fiber synapses is circumscribed and reversible in a slow-channel syndrome model
Autor: | Robert L. Wollmann, Bhupinder P. S. Vohra, Christopher M. Gomez, Jason S. Groshong, Roberto Zayas |
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Rok vydání: | 2006 |
Předmět: |
medicine.medical_treatment
Muscle Fibers Skeletal Excitotoxicity Neuromuscular junction Apoptosis Mice Transgenic medicine.disease_cause lcsh:RC321-571 Mice Motor Endplate Channelopathy medicine Animals Humans Receptors Cholinergic Acetylcholine receptor Muscle Skeletal lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Caspase Myasthenic Syndromes Congenital biology integumentary system Disease Models Animal medicine.anatomical_structure Neurology nervous system Mutation biology.protein Cholinergic Calcium Axotomy Neuroscience tissues |
Zdroj: | Neurobiology of Disease, Vol 23, Iss 2, Pp 462-470 (2006) |
ISSN: | 0969-9961 |
Popis: | In the slow-channel syndrome (SCS) mutant acetylcholine receptors elicit calcium overload and myonuclear degeneration at the neuromuscular junction (NMJ), without muscle fiber death. Activated caspases are present at SCS motor endplates. We hypothesized that SCS represents a limited form of apoptosis. We found condensed chromatin and occasional single-strand DNA nicks in degenerating synaptic nuclei. Cleaved forms of caspases-3 and -9 were present in mouse SCS muscle homogenates and were specifically localized to NMJs. Finally, interruption of cholinergic activity by axotomy markedly reduced NMJ caspase activity and improved the morphological features of apoptosis at NMJs. These results demonstrate that in SCS processes leading to apoptosis may remain compartmentalized and reversible. Use of cysteine protease inhibitors may aid in treatment of this and other dystrophic muscle and excitotoxic disorders. Identification of extrasynaptic factors that prevent the spread of apoptosis in SCS muscle fibers may aid in developing treatments for neurological disorders characterized by excitotoxicity or apoptosis. |
Databáze: | OpenAIRE |
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