title: Adiponectin receptor-mediated signaling ameliorates cerebral cell damage and regulates the neurogenesis of neural stem cells at high glucose concentrations: an in vivo and in vitro study.
abstract: In the central nervous system (CNS), hyperglycemia leads to neuronal damage and cognitive decline. Recent research has focused on revealing alterations in the brain in hyperglycemia and finding therapeutic solutions for alleviating the hyperglycemia-induced cognitive dysfunction. Adiponectin is a protein hormone with a major regulatory role in diabetes and obesity; however, its role in the CNS has not been studied yet. Although the presence of adiponectin receptors has been reported in the CNS, adiponectin receptor-mediated signaling in the CNS has not been investigated. In the present study, we investigated adiponectin receptor (AdipoR)-mediated signaling in vivo using a high-fat diet and in vitro using neural stem cells (NSCs). We showed that AdipoR1 protects cell damage and synaptic dysfunction in the mouse brain in hyperglycemia. At high glucose concentrations in vitro, AdipoR1 regulated the survival of NSCs through the p53/p21 pathway and the proliferation- and differentiation-related factors of NSCs via tailless (TLX). Hence, we suggest that further investigations are necessary to understand the cerebral AdipoR1-mediated signaling in hyperglycemic conditions, because the modulation of AdipoR1 might alleviate hyperglycemia-induced neuropathogenesis.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.affiliation: 1] Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, South Korea [2] BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Department of Psychiatry, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: C-H
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: H-T
authors.initials: HT
authors.lastname: Song
authors.affiliation: 1] Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, South Korea [2] BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: J E
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005786:Gene Expression Regulation; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D061251:Primary Cell Culture; D054419:Receptors, Adiponectin / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C490258:Nr2e1 protein, mouse; D054419:Receptors, Adiponectin; D018160:Receptors, Cytoplasmic and Nuclear; D016159:Tumor Suppressor Protein p53; C475419:adiponectin receptor 1, mouse; D005947:Glucose