2003 Fiscal Year Final Research Report Summary
Does ethanol-induced lipid metabolism dysfunction aggravate symptoms of dementia?
| Project/Area Number |
14570936
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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 | Sapporo Medical University |
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Principal Investigator |
IKEDA Hiroshi Sapporo Med.Univ.Sch.Med., Dept.Neuropsychiatry, Assistant Prof., 医学部, 講師 (30232193)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Taku Sapporo Med.Univ.Sch.Med., Dept.Neuropsychiatry, Instructor, 医学部, 助手 (60347169)
YAMAMOTO Megumi Sapporo Med.Univ.Sch.Med., Dept.Neuropsychiatry, Assistant Prof., 医学部, 講師 (90347170)
SAITO Toshikazu Sapporo Med.Univ.Sch.Med., Dept.Neuropsychiatry, Professor, 医学部, 教授 (50128518)
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| Project Period (FY) |
2002 – 2003
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| Keywords | alcohol dependence / Alzheimer's disease / annexin IV / CREB / NF κ-B / BDNF / ApoE |
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| Research Abstract |
Ethanol has been shown to induce apoptosis in normal tissues including neural tissues. It has also reported that ethanol has an aspect of aggravate symptoms of dementia. Our previous studies suggest that the quantitative reduction of certain type of adenylyl cyclase is related to the features of alcohol dependence and Alzheimer's disease indicating that cAMP-mediated signal transduction is disordered in those brains. In the present study, we measured the ethanol-induced cytotoxicity and the quantitative alteration of brain-derived neurotrophic factor(BDNF), which is one of the important target genes of CREB. Using SH-SY5Y cells, it was revealed that the amount of BDNF was decreased by the exposure to ethanol in the cultured cells, whereas the activity of NF κ-B was increased. We next investigated the effects of ethanol on the survival on primary cultured rat cortical neurons and the differentiation of neural stem cells(NSCs). Ethanol exposure decreased the survival of neurons. Both ins
… More
ulin-like growth factor-1(IGF-1) and BDNF promoted neuronal differentiation of NSCs in a dose-dependent-manner, and the inhibition of NSC differentiation by ethanol was suppressed by IGF-1 and BDNF. Ethanol may inhibit NSC differentiation through alteration of cellular pathways related to neurotrophic factors. Furthermore, the isoform specific effects of apoE on the ethanol-induced cytotoxicity were identified. It was shown that the addition of apoE4 diminish the ethanol-induced cytotoxicity, whereas the presence of neither apoE2 nor apoE3 inhibits the cytotoxicity by the exposure of ethanol. The precise mechanisms of promoting effect of apoE on ethanol-induced cell damage have yet to be clarified and further investigations will be required. However, the present study suggests that the ethanol-induced alterations of second messengers below receptors effect on intracellular transfactors and alternate structure of neural network through expression of genes and intracellular proteins, contributing to the development of cognitive disturbances. To the contrary, induction of differentiation into neurons, recovery of number of neurons and promotion of remodeling of neural network may be applied to the treatment of alcoholism and Alzheimer's disease. It seems possible to broaden our choices of therapeutic strategies by approaching to those illnesses regarding them as a cognitive disorders caused by dysfunctions of lipid metabolism and neural network system. Less
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