1998 Fiscal Year Final Research Report Summary
Neuron-Glia Interaction and Neural Network Function Involved in Ischemic Brain Damage.
| Project/Area Number |
09680817
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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 |
神経・脳内生理学
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| Research Institution | Hamamatsu University School of Medicine (1998)
Nagoya City University (1997) |
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Principal Investigator |
FUKUDA Atsuo Hamamatsu University School of Medicine, Physiology, Professor, 医学部, 教授 (50254272)
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| Co-Investigator(Kenkyū-buntansha) |
NISHINO Hitoo Nagoya City Univ.Med.Sch., Physiology, Professor, 医学部, 教授 (60073730)
UCHIDA Katsuhisa Hamamatsu Univ.Sch.Med., Physiology, Res.Assoc., 医学部, 助手 (10168693)
SAMEJIMA Michikazu Hamamatsu Univ.Sch.Med., Physiology, Assoc.Prof., 医学部, 助教授 (80135251)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Intracellular Cl^- / Cl^- transporter / MEQ / Intracellular Ca^<2+> / Na^+-Ca^<2+> exchanger / Cerebral ischemia / Mitochondria / Glia |
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| Research Abstract |
1. Slices of neocortex taken from P7-14 rats were labeled with fura-2. The [Ca^<2+>] _i was monitored pyramidal cells during O_2-glucose deprivation. Neurons in layer II/III showed significantly greater increases in [Ca^<2+>] _i than those in layers IV, V, or VI.The laminar difference in terms of the [Ca^<2+>] _i increases was primarily mediated by NMDA receptors. GABA might also act to increase [Ca^<2+>] _i during O_2-glucose deprivation. After a reduction in the Cl^- gradient, GABA induced a large [Ca^<2+>] _i increase mediated by NMDA receptor-channels. This indicates that a loss of the normal Cl^- gradient during ischemia might underlie the reduction and/or reversal of the GABAergic inhibition. Thus GABA may play an aggravating role in excitotoxicity if a shift in the Cl^- equilibrium potential occurs during cerebral ischemia.
2. We have developed an optical imaging method of [Cl^-] _i in brain slices using 6-methoxy-N-ethylquinolinium iodide (MEQ). Slices of neocortex taken from P1
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0-14 rats were labeled with MEQ ; [Cl^-] ^i was monitored in individual neurons during O_2-glucose deprivation. A slight decrease followed by rather abmpt increase in [Cl^-] _i was induced by O_2-glucose deprivation. The former was mediated by an inhibition of Na^+, K^+-2Cl^- cotransporter. Such a shift in [Cl^-] _i induced by O_2-glucose deprivation would alter the GABAergic inhibition and may result in imbalance between inhibitory and excitatory systems.
3.3-NPA-induced [Ca^<2+>] _i transients in mixed glial/neuronal cultures were investigated using fura-2.3-NPA irreversibly increased [Ca^<2+>] _i in astrocytes, but significantly to alesser extent in neurons. The [Ca^<2+>] _i increase in astrocytes was primarily promoted by a reverse operation of the Na^+-Ca^<2+> exchanger system, whereas in neurons, it was mediated by a different mechanism. In addition, 3-NPA killed 9% of astrocytes, while only 4% of neurons. This astrocytic cell death was preceded by blebbing of membranes and by abrupt [Ca^<2+>] _i surge following sustained [Ca^<2+>] _i increase. The results indicate that astrocytes are more vulnerable than neurons to 3-NPA-induced cellular Ca^<2+> overload and toxicity. Differential metabolism in energy production between astrocytes and neurons were suggested. Less
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