Research on the manifestation mechanism of Parkinsonian tremor : On the role of serotonergic neuron of raphe nucleus.

帕金森震颤的表现机制研究：中缝核5-羟色胺能神经元的作用。

• 批准号: 10470283
• 负责人: TAKAHASHI Toshio
• 金额: $ 3.78万
• 依托单位: HIROSAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470283/
• 关键词: Parkinson's disease; resting tremor; raphe nuclei; serotonin; clopamine; experimental tremor; MPTP

PURPOSE: The main lesion of Parkinson's disease is the selective neuronal death of the nucleus niger (clopaminergic neuron) and locus ceruleus of the midbrain (noradrenergic neuron). However, we cannot necessarily explain all the manifestations and mechanism of resting tremor by these sites of damage alone. The ventromedial tegmentum (VMT) is known as the region that includes Parkins-onian tremor in the monkey. We have reported that great numbers of cells in the nucleus niger and dorsal raphe nucleus were labeled by the local injection of horseraclish peroxidase into VMT in both of monkeys and cats . It is the purpose of this research to clarify that damages or not only the nucleus niger but also raphe nucleus serotonergic neurons are involved in the manifestation of tremor. METHOD : Fifteen mature cats were divided into two groups : one is a coagulation group of the dorsal raphe nucleus, and the other is a non-coagulation group. In the coagulation group, damage of the nucleus niger do … More pamine system is induded by MPTP, after the destruction of the dorsal raphe nucleus using a stereotactic coagulation technique. In both groups, MPTP (3 mg/kg/day) was injected intramuscularly every other day 8〜14 times in total. The reactions after injection were then recorded and analyzed in video and electromyogram. The coagulated lesions were confirmed in the serial-section samples of the brain. RESULT : Though there was a difference of severity, rigidity was observed in both groups after MPTP administration. In the three cats in which the dorsal raphe nucleus was accurately included in the coagulated lesion, the tremor was observed after the seventh or eighth repetitive administration of MPTP. The tremor occurred in the resting position and lightly bending position of the limbs, and its cycle was similar to Parkinsonian tremor of 4〜6 Hz. In two cats, the tremor appeared throughout the 15〜40 minutes after MPTP administration, and gradually dissappeared. In one other cat, a similar tremor was observed after the eighth administration of MPTP, even on the clay when MPTP was not administered. In the cats of which the dorsal raphe nucleus was not destroyed accuratehr by coagulation, the tremor did not develop. CONCLUSION : Even in the cat, it was possible to create a resting tremor that is similar to Parkinsonian tremor. From the facts described above, we may conclude that damages both of the raphe nucleus serotonin system and the nucleus niger dopamine system may be involvecl in the mechanism for Parkinsonian tremor . Less

目的：帕金森病的主要病变是黑核（氯胺能神经元）和中脑蓝斑（去甲肾上腺素能神经元）的选择性神经元死亡。然而，我们不能仅仅通过这些部位的损伤来解释静息性震颤的所有表现和机制。腹内侧被盖层（VMT）是猴子帕金森震颤的区域。我们已经报道了在猴子和猫的VMT中局部注射马辣过氧化物酶可以标记大量的黑核和中缝背核细胞。本研究的目的在于阐明震颤的表现不仅涉及黑核，而且涉及中隔核5 -羟色胺能神经元的损伤。方法：将15只成年猫分为中缝背核凝血组和非凝血组。用立体定向凝固技术破坏中缝背核后，MPTP诱导了更多的多巴胺系统。两组均每隔一天肌肉注射MPTP (3 mg/kg/d)，共8 ~ 14次。然后用视频和肌电图记录和分析注射后的反应。在脑的连续切片样本中证实了凝固病灶。结果：两组患者经MPTP治疗后，均出现骨僵硬，但严重程度有差异。在中缝背核准确包含在凝固病灶内的3只猫中，第七次或第八次MPTP重复给药后观察到震颤。震颤发生在四肢的静止位置和轻度弯曲位置，其周期与帕金森震颤相似，为4 ~ 6 Hz。2只猫在MPTP给药后15 ~ 40分钟出现震颤，并逐渐消失。在另一只猫中，在第八次施用MPTP后观察到类似的震颤，即使在没有施用MPTP的粘土上也是如此。在那些中缝背核没有被凝血准确破坏的猫身上，震颤没有发生。结论：即使在猫身上，也有可能产生与帕金森震颤相似的静息性震颤。根据上述事实，我们可以得出结论，中隔核血清素系统和黑核多巴胺系统的损害可能参与了帕金森震颤的机制。少