title: Characterization of neuronal and astroglial responses to ER stress in the hippocampal CA1 area in mice following transient forebrain ischemia.
abstract: Transient forebrain ischemia has been shown to cause neuronal injury in the CA1 area of the hippocampus in mice. In addition to neuronal injury, astrocytes in area CA1 undergo apoptosis under ischemic conditions. Although failure of impaired astrocytes to take up glutamate is thought to contribute to the pathogenesis of cerebral ischemia, the molecular mechanism underlying this phenomenon remains unexplored. In the present study, we investigated neuronal and astroglial responses to endoplasmic reticulum (ER) stress, which is an important sequela of transient forebrain ischemia in the hippocampus of mice. Cellular injury was observed in area CA1 of the hippocampus 72h after reperfusion, and ssDNA positivity was detectable in some glial cells as well as neurons in this area. An increase of 78-kDa glucose-regulated protein (GRP78), an indicator of ER stress, was detected in pyramidal neurons and astrocytes in this area after the insult. Immunohistochemical analysis showed that caspase-12 was increased in pyramidal neurons and astrocytes located in the extrapyramidal cell layer. Immunoreactivity for C/EBP homologous protein (CHOP) was increased significantly in pyramidal cells but not in astrocytes. These results suggest that astrocytes as well as pyramidal neurons in area CA1 undergo apoptosis through an ER stress-dependent mechanism after ischemia. Unlike the situation in neuronal apoptosis, CHOP does not play a role in the cell death of astrocytes.
authors.affiliation: Research Unit of Pharmacology, Department of Clinical Pharmacy, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Osada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kosuge
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ishige
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology; D013312:Stress, Physiological / Q000502:physiology*