Apelin Deficiency Accelerates the Progression of Amyotrophic Lateral SclerosisReportar como inadecuado




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Amyotrophic lateral sclerosis ALS is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor VEGF-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1G93A displayed the disease phenotypes earlier than SOD1G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H2O2-induced neuronal death in primary neurons. These results suggest that apelin-APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS.



Autor: Atsushi Kasai , Toshihiko Kinjo, Rie Ishihara, Ikumi Sakai, Yuki Ishimaru, Yasuhiro Yoshioka, Akiko Yamamuro, Kumiko Ishige, Yosh

Fuente: http://plos.srce.hr/



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