| Project/Area Number |
13680882
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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 |
Neuroscience in general
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| Research Institution | Teikyo University |
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Principal Investigator |
KUWANA Shin-ichi Teikyo University, School of Medicine, Lecturer, 医学部, 講師 (70129998)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Yasumasa Keio University, School of Medicine, Lecturer, 医学部, 講師 (80160688)
SUGAWARA Yoshiko Teikyo University, school of Medicine, Lecturer, 医学部, 講師 (20082191)
長井 孝紀 慶應大学, 医学部, 教授 (50130026)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | GABA / Respiration / GAD67 / Knock-out mice / Respiratory rhythm / Brainstem-spinal cord / Neuronal network / Neonatal mice / GAD / 高炭酸ガス応答 / 低酸素応答 / 口蓋裂 |
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| Research Abstract |
To examine the role of GABA in the respiratory rhythm and pattern generation in neonatal mice, we analyzed the function of the respiratory control system of 67-kDa isoform of glutamic acid decarboxylase (GAD67)-deficient neonatal mice. In these mutant (GAD67-/-) mice, GABA levels in the brainstem were reduced to about 30 % of those in wild-type (GAD67+/+) mice. In in vivo preparations, ventilatory parameters were analyzed by whole body plethysmography and electromyography of intercostal muscles. GAD67-/-mice exhibited abnormal respiratory' patterns, i.e., irregular respiratory rhythm, and periodic gasp-like respiration followed by shallow breathing with short inspiratory duration and apnea. In in vitro GAD67-/-brainstem-spinal cord preparations, inspiratory C4 burst duration was shorter than that in GAD67+/+ preparations. Whole cell recordings revealed that activities of inspiratory neurons in the ventral medulla of GAD67-/-mice were characterized by a short depolarization period and a paucity of firing during the inspiratory phase. Superfusion of the in vitro GAD67-/-preparation with 10 g M GABA prolongedC4 burst duration and partly restored a normal pattern of inspiration, although the restoration was limited. These results indicate that reduced GABA levels during the perinatal period induce malfunction in the respiratory control system. We suggest that GABAergic transmission is not essential for basic respiratory rhythm generation but plays an important role in the maintenance of regular respiratory rhythm and normal inspiratory pattern in neonatal mice.
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