2004 Fiscal Year Final Research Report Summary
The monoaminergic modulation of spinal motor function and the alteration in the motor disease
| Project/Area Number |
15590134
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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 |
Medical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
ONO Hideki Nagoya City University, Faculty of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (00080200)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Mitsuo Nagoya City Univeisity, Faculty of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 助教授 (20360026)
HONDA Motoko Nagoya City University, Faculty of Pharmaceutical Sciences, Reserch Assistant, 大学院・薬学研究科, 助手 (30297626)
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| Project Period (FY) |
2003 – 2004
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| Keywords | descending monoaminergic systems / noradrenaline / serotonin / spinal motors stem / motor disease / spinocerebellar atrophy |
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| Research Abstract |
The descending noradrenergic and serotonergic systems modulate the function of the spinal α-motoneurons which control movements of body and limbs. However, the function and changes in neuronal disease are unclear. In the present study, the following results were obtained.
1. Serotonergic agonists have been shown both to increase and decrease spinal motor transmission. Motoneurons possess somatodendritic serotonin (5-HT)_2 receptors, which account for the increased excitability. However, it is unclear which receptor subtypes mediate the inhibitory effects on spinal reflexes. We showed that 5-HT_<1B> and 5-HT_<1D> receptors located in the spinal cord mediate the 5-HT-induced inhibition of spinal reflexes.
2. Spinal reflexes and recurrent and presynaptic inhibitions in streptozotocin (STZ)-induced diabetic rats were examined. The recurrent inhibition which is mediated by glycine was depressed in diabetic rats. In addition, the inhibitory effect of 5-HT was decreased in those rats. These res
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ults show that the diabetogenic degeneration occurred in not only sensory but also motor systems.
3. The relationships between ataxia and the monoamines concentrations of central nervous systems were examined in spinocerebellar atrophy (SCD) model mice. Two SCD model mice, rolling mouse Nagoya (RMN) and Ara-C mice which were produced by the administration of cytosine arabinoside on 2, 3, 4 days after birth, were used. The concentrations of monoamines were increased in CNS of these SCD model mice. The repeated administration of taltirelin hydrate, which is clinically used for SCD treatment, improved ataxia, but did not affect the monoamines concentration of CNS in RMN and Ara-C mice.
4. We showed that the noxious stimuli-evoked flexor reflex of mice were composed from Aδ-fiber mediated short-latency and C-fiber-mediated long-latency withdrawal movements. These withdrawal movements are facilitated by repeated stimulation, it is called wind-up. In STZ-induced diabetic mice, the wind-up of C-fiber-mediated movement, but not Aδ-fiber-mediated one, was enhanced significantly. Less
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