2005 Fiscal Year Final Research Report Summary
A genetic animal model with spontaneous seizures : Noda epileptic rats.
| Project/Area Number |
15591218
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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 |
Psychiatric science
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
KANAI Hirohiko Shiga University of Medical Science, MD, PhD, assistant professor, 医学部, 講師 (30293830)
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| Co-Investigator(Kenkyū-buntansha) |
KUROKAWA Kiyoshi Shiga University of Medical Science, MD, Phd, associate professor, 医学部, 助教授(准教授) (40215083)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Epilepsy / Hippocampus / Animal model / Apoptosis / Corticosterone / Circadian rhythm / Serotonin / Rat |
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| Research Abstract |
Research I
We previously demonstrated the increased immunoreactivities of neuropeptide Y(NPY-IR), an endogenous anti-convulsive agent, in several epileptic models, including noda epileptic rats(NERs). NERs have an advantage to study the pathological change at the onset of spontaneous seizures, because NERs exhibit the age-related seizure development. In this study, we examined the temporal expression of the mRNA of BDNF/trkB in the NERs-hippocampus after a spontaneous seizure using in situ reverse transcription-polymerase chain reaction(RT ISIT).
Brain-derived neurotrophic factor(BDNF) and its receptors, trkB, have been considered to associate with the epileptogenesis and the mossy fiber sprouting, a histological hallmark of the epileptogenesis. However, it remains unclear whether the BDNF/trkB signaling is pro-convulsive or anti-convulsive. To explore roles of the BDNF/trkB signaling in the epileptogenesis in noda epileptic rats (NERs), we examined the alteration of the mRNA expressions
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of BDNF and trkB in the hippocampus of NERs after a spontaneous seizure using RT-ISH. We also examined the nature of the mossy fiber sprouting in NERs using Timm's staining. NERs aged 15 weeks(W) with spontaneous tonic-clonic seizures were used. Unexpectedly, NERs showed significantly lower levels of bdnf and trkB mRNA in the CA3 subfield than the Wistar : Crj rats. Further, a single spontaneous seizure itself did not directly alter the bdnf and trkB mRNA until 12 h after seizures. In the histological examination in the hippocampus of NERs, there were no apparent neuronal damages and minimal changes concerning mossy fiber sprouting in the CA3 and the dentate gyrus. The present study suggests that in 15 Waged NERs, the BDNF/trkB signaling does not facilitate the seizure susceptibility and the mossy fiber sprouting.
Research 2
A rapid elevation in the level of endogenous corticosterone(CORT) functions in the stress response associated with the hypothalamus-pituitary-adrenal axis, and it has been well documented that high levels of CORT play neurotoxic roles in the hippocampus. Both aging and the circadian rhythm possibly affect the sensitivity to CORT, although their endogenous modifications in the CORT-mediated events remain unclear. To explore the influence of age or circadian time on hippocampal vulnerability to excess CORT, we examined the relative mRNA expression of bcl-2 and bax in the dentate gyrus(DG) and the CAI subfield, compared with the CA3 as an internal standard, after acute CORT administration using in situ RTPCR. Male rats aged 10 weeks(young) or 6 months(adult) were treated with CORT at 0800 or 2000 hours. The bcl-2 to bax mRNA ratio in the dentate gyros(DG) was significantly decreased 2 h after CORT exposure in the young rats treated at 0800 or 2000 hours. In the adult rats, the treatment with CORT at 0800 hours significantly decreased the bcl-2 to bax ratio, whereas the treatment at 2000 hours was ineffective ; the discrepancy between the treatment time points was apparent in adult rats, but not in young rats. Our results emphasize the importance of circadian time as well as age as a factor influencing the stress paradigm. Less
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Research Products
(2 results)
