2012 Fiscal Year Final Research Report
Mechanisms of lipid metabolism disorder in diabetic brain
| Project/Area Number |
23689047
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SUZUKI Ryo 東京大学, 医学部附属病院, 特任講師 (20396732)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 糖尿病 / 認知機能 / コレステロール合成 / 脳 / SCAP / SREBP-2 / ノックアウトマウス |
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| Research Abstract |
Decrease of SCAP, a sterol sensor molecule, was observed in the brain of STZ-induced severe diabetes mouse model. Homozygous disruption of the Scap gene in the brains of mice caused perinatal lethality associated with microcephaly. Mice with haploinsufficiency of Scap in the brain showed reduction in brain cholesterol synthesis, similar to what was observed in diabetic mice. This resulted in impaired synaptic transmission, as measured by decreased long-term potentiation, and was associated with behavioral and cognitive changes. Thus, reduction of SCAP and the consequent suppression of cholesterol synthesis in the brain may play an important role in the increased rates of cognitive decline observed in diabetic states.
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