title: Increased vulnerability of hippocampal CA1 neurons to hypoperfusion in ataxia and male sterility (AMS) mouse.
abstract: The nna1 gene mutation is associated with spontaneous degeneration of cerebellar Purkinje cells and germ cells in Ataxia and Male Sterility (AMS) mouse. Since nna1 is also expressed in hippocampal neurons, we investigated their vulnerability to hypoperfusion in AMS mouse. Eight-week-old male wild type (WT) and AMS mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 10 min and sacrificed 1, 3, 7 and 28 days after BCCAO. Nissl staining revealed the neuronal cell loss and pyknotic change in the CA1 of AMS mice. TUNEL(+) apoptotic cells were found in the area at 7 days in AMS mice. Bcl-2 mRNA and protein in WT hippocampus were increased, while they were not increased in AMS. Bax mRNA was increased in AMS. Moreover, Bax activation was immunohistochemically demonstrated only in AMS at 3 and 7 days after BCCAO. An oxidative DNA damage marker, 8-hydroxydeoxyguanosine-positive cells were increased in both strains at 1 day; decreased in WT at 3 days but remained high in AMS. BCCAO increased glutathione, an antioxidant, in WT, but not in AMS at 3 days. The mRNA level of mitochondrial uncoupling protein 2, a regulator of oxidative stress, was increased only in WT at 1 day. Nna1 mRNA was similarly expressed in WT and AMS, but the protein was undetectable in AMS. Thus, our results indicate the increased vulnerability of hippocampal CA1 neurons of AMS mice to cerebral hypoperfusion could be due to an imbalance between oxidative stress and antioxidative defense system.
authors.affiliation: Department of Laboratory Medicine, Shimane University School of Medicine, Izumo 693-8501, Japan.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Liang
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
authors.forename: Abdullah Md
authors.initials: AM
authors.lastname: Sheikh
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Shingo
authors.initials: S
authors.lastname: Mitaki
authors.forename: Asuka
authors.initials: A
authors.lastname: Araki
authors.forename: Riruke
authors.initials: R
authors.lastname: Maruyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001259:Ataxia / Q000150:complications / Q000235:genetics / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000601:surgery; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007248:Infertility, Male / Q000150:complications / Q000235:genetics / Q000473:pathology*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000150:complications / Q000473:pathology*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008818:Mice, Neurologic Mutants; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D007473:Ion Channels; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C420042:Agtpbp1 protein, mouse; D019204:GTP-Binding Proteins; D005978:Glutathione