title: Apelin deficiency accelerates the progression of amyotrophic lateral sclerosis.
abstract: 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 SOD1(G93A) 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 SOD1(G93A) mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1(G93A) displayed the disease phenotypes earlier than SOD1(G93A) 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 H(2)O(2)-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.
authors: Department of Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan. akasai@mednet.ucla.edu
authors: Atsushi
authors: A
authors: Kasai
authors: Toshihiko
authors: T
authors: Kinjo
authors: Rie
authors: R
authors: Ishihara
authors: Ikumi
authors: I
authors: Sakai
authors: Yuki
authors: Y
authors: Ishimaru
authors: Yasuhiro
authors: Y
authors: Yoshioka
authors: Akiko
authors: A
authors: Yamamuro
authors: Kumiko
authors: K
authors: Ishige
authors: Yoshihisa
authors: Y
authors: Ito
authors: Sadaaki
authors: S
authors: Maeda
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D000073861:Apelin; D018450:Disease Progression; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D009046:Motor Neurons / Q000473:pathology; D018696:Neuroprotective Agents; D012333:RNA, Messenger / Q000032:analysis; D013116:Spinal Cord / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: C115436:APLN protein, human; D000073861:Apelin; D036341:Intercellular Signaling Peptides and Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger