title: Accumulation of autofluorescent storage material in brain is accelerated by ischemia in chloride channel 3 gene-deficient mice.
abstract: Autofluorescent storage material (ASM) is an aging pigment that accumulates during the normal course of senescence. Although the role of ASM has yet to be fully elucidated, ASM has been implicated in age-related neurodegeneration. In this study, we determined the level of ASM in chloride channel 3 (ClC-3) gene-deficient (KO) mice both in response to aging and following mild global ischemia. To understand the mechanism of action of the ASM, mice subjected to ischemia were treated with the cyclooxygenase (COX) inhibitor indomethacin or with the noncompetitive glutamate receptor antagonist MK-801. ClC-3 KO mice displayed age-related neurodegeneration of the neocortex as well as the hippocampus. The cortical layers in particular granular layers became thinner with aging. ASM accumulated in the brains of ClC-3 KO mice was increased seven- to 50-fold over that observed in the corresponding regions of their wild-type littermates. Young wild-type mice survived longer than age-matched ClC-3 KO mice after permanent global ischemia. However, in the case of older animals, the survival curves were similar. The ASM also increased four- to fivefold 10 days after mild global ischemia, an effect that was suppressed by treatment with indomethacin and MK-801. These results suggest that temporary ischemia might trigger a process similar to aging in the brain, mimicking the effect of age-related neurodegenerative diseases.
authors: Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
authors: Hirokazu
authors: H
authors: Ohtaki
authors: Kenji
authors: K
authors: Ohara
authors: Dandan
authors: D
authors: Song
authors: Kazuyuki
authors: K
authors: Miyamoto
authors: Tomomi
authors: T
authors: Tsumuraya
authors: Sachiko
authors: S
authors: Yofu
authors: Kenji
authors: K
authors: Dohi
authors: Shigeru
authors: S
authors: Tanabe
authors: Sei
authors: S
authors: Sasaki
authors: Shinichi
authors: S
authors: Uchida
authors: Masaji
authors: M
authors: Matsunaga
authors: Seiji
authors: S
authors: Shioda
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002566:Ceroid / Q000032:analysis*; D018118:Chloride Channels / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D007150:Immunohistochemistry; D008062:Lipofuscin / Q000032:analysis*; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D061848:Optical Imaging
chemical_list: D002566:Ceroid; D018118:Chloride Channels; C115376:ClC-3 channel; D008062:Lipofuscin