2002 Fiscal Year Final Research Report Summary
Roles of astroglial energy metabolism in ischemic neuronal cell damage: an implication for the treatment of cerebral ischemia
| Project/Area Number |
11470149
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Keio University |
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Principal Investigator |
TAKEDA Hidetaka Department of Neurology, Instructor, 医学部, 助手 (70245489)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Shigeaki Department of Neurology, Instructor, 医学部, 助手 (50276242)
DEMBO Tomohisa Department of Neurology, Instructor, 医学部, 助手 (50306700)
ITOH Yoshiaki Department of Neurology, Instructor, 医学部, 助手 (90265786)
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| Project Period (FY) |
1999 – 2002
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| Keywords | ASTROCYTE / NEURON / GLUCOSE / GLYCOGEN / PYRUVATE / LACTATE / MTT / Alamar Blue |
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| Research Abstract |
1) Persistent activation of voltage-sensitive sodium channels results in Na^+ influx into rat cultured neurons and induces neuronal cell damage. Sodium ionophore also induces Na^+ -induced neuronal damage.
2) Na^+ influx causes astroglial cell damage via its mitochondrial dysfunction. The mechanism by which Na^+ influx induces cell damage in astroglia is different from that in neurons.
3) 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction is interpreted to be indicative of cellular metabolic activity. MTT specific activity of astroglia was much higher than that of neurons. In astroglia, MTT reduction reflects mainly cytosolic redox activity and is dependent on glyceraldehyde 3-phosphate dehydrogenase. In neurons, pyruvate dehydrogenase supports MTT reduction more effectively than glucose or lactate, even though both of these substrates can produce NADH and pyruvate.
4) Glucose is the sole energy source of the brain. In brain, only astrocytes can store glucose as intracellular glycogen and utilize it when glucose supply is limited. We examined the effect of acute or chronic exposure to glucose depleted condition on intracellular glycogen content and the reduction of Alamar Blue, an indicator of cellular energy metabolism, in rat cultured astroglia. Obtained results suggest that astroglial energy production becomes more dependent on the TCA cycle when extracellular glucose and intracellular glycogen are not available.
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