2007 Fiscal Year Final Research Report Summary
Apoptosis of motor neurons after spinal cord injury
| Project/Area Number |
18591575
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Akita University |
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Principal Investigator |
SUZUKI Akira Akita University, Akita University School of Medicine, Assistant Professor (10311573)
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| Co-Investigator(Kenkyū-buntansha) |
SUGAWARA Taku Akita University, Akita University School of Medicine, Lecturer (80241660)
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| Project Period (FY) |
2006 – 2007
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| Keywords | spinal cord injury / motor neurons / apoptosis / oxidative stress / superoxide |
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| Research Abstract |
Spinal motor neurons are selectively vulnerable after spinal cord injury (SCI). Recent studies suggest they undergo apoptosis after caspase activation through a mitochondria-dependent apoptosis pathway, and that oxidative stress after SCI is likely to play a role. However, other signaling pathways of apoptosis that involve mitochondria have not been thoroughly studied after SCI. Apoptosis-inducing factor (AIF) and endonuclease G (EndoG) are mitochondrial apoptogenic proteins that are capable of inducing neuronal apoptosis when translocated from mitochondria to nuclei through a caspase-independent pathway. In this study, we examined translocation of these proteins and apoptotic cell death of motor neurons. The role of oxidative stress was also studied using transgenic (Tg) rats that overexpress the intrinsic antioxidant copper/zinc-superoxide dismutase (SOD1). Western blots and an activity assay demonstrated that a greater amount of SOD1 and higher activity of SOD presented in mitochondria of Tg rats compared with wild-type (Wt) rats. Immunohistochemistry and Western blots showed translocation of EndoG and AIF from mitochondria to nuclei in motor neurons 1 day after SCI in both groups of rats. However, there was significantly less translocation of EndoG in the Tg rats compared with the Wt rats. Less apoptotic cell death was detected in the Tg rats than in the Wt rats 3 days after SCI. These results suggest that translocation of EndoG and AIF from mitochondria to nuclei may initiate a caspase-independent pathway of apoptosis. An increased level of SOD1 in mitochondria conceivably reduces oxidative stress, thereby attenuating EndoG translocation, and resulting in reduction of caspase-independent apoptosis.
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[Journal Article] Model mice for mild-form glycine encephalopathy: behavioral and biochemical characterizations and efficacy of antagonists for the glycine binding site of N-methyl D-aspartate receptor.2008
Author(s)
Kojima-ishii K, Kure S, Ichinohe A, ShinkaT, NarisawaA, Komatsuzaki S, Kanno J, Kamada F, Aoki Y, Yokoyama H, Oda M, Sugawara T, Mizoi K, Nakahara D, Matsubara Y.
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Journal Title
Pediatr Res 64
Pages: 228-233
Description
「研究成果報告書概要(欧文)」より
