2012 Fiscal Year Final Research Report
Neurotrophic factors and cognitive function after alcohol intoxication in mice model
| Project/Area Number |
22590636
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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 |
Legal medicine
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Keywords | Neurotrofic factor / Ethanol / Acetaldehyde / Knockout mice / Memory |
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| Research Abstract |
Here we investigated the effects of ethanol (EtOH) and acetaldehyde (AcH) on behavior,and mRNA levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and c-fos at 30 min after EtOH in Aldehyde dehydrogenase 2 knock (Aldh2-KO), Apolipoprotein E knockout (ApoE-KO) and wild type (WT) mice. Eight-arm-radial maze and Morris-water maze showed that 1) 2.0 g/kg EtOH impaired spatial memory in all three strains, while lower doses did not have consistent memory effects, 2) a probe trial(drug-free state) showed a sustained memory impairment in mice that had received 2.0 g/kg EtOH previously, regardless of strain, 3) ApoE-KO mice learned more slowly than WT mice, and the Aldh2-KO mice learned more quickly.Real time PCR showed that 1) EtOH increased c-fos mRNA expression in ALDH2-KO (1 and 2g/kg) and WT (2.0 g/kg), 2) 2.0 g/kg of EtOH decreased ChAT mRNA in Aldh2-KO mice, while acetylcholinesterase mRNA expression was increased in both strains, 3) acute EtOH failed to alter the mRNA levels of NGF and BDNF and 4)Aldh2-KO mice showed a distinctly lower level of ChAT mRNA and a higher level of NGF mRNA versus WT mice. Our observation suggests that high EtOH and AcH can alter cholinergic markers and this effect did not modify the levels of NGF and BDNF.
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