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中脑黑核（氯巴胺能神经元）和蓝斑（去甲肾上腺素能神经元）的选择性神经元死亡，但是，我们不一定能解释这些部位的静息性震颤的所有表现和机制。腹内侧被盖（VMT）被称为包括猴子帕金森震颤的区域。通过在猴子和猫的VMT中局部注射辣根过氧化物酶来标记黑核和中缝背核中的细胞数量。本研究的目的是阐明不仅损害黑核而且损害中缝核。方法：将十五只成年猫分为两组：一组是中缝背核凝固组，另一组是中缝背核凝固组。在非凝固组中，在使用立体定向凝固技术破坏中缝背核后，MPTP 引起了黑核多巴胺系统的损伤。每隔一天肌内注射一次，共8至14次，然后通过视频和肌电图记录和分析注射后的反应，以确认连续切片样本中的凝固病变。结果：尽管在MPTP给药后两组中观察到了严重程度的差异，但在中缝背核准确地包含在凝固病变中的三只猫中，在第七次或以后观察到震颤。 MPTP第8次重复给药时，震颤发生在四肢的静息位和轻微弯曲位，其周期与帕金森病震颤相似，两只猫的震颤出现在整个过程中。给予 MPTP 15-40 分钟后，在另一只猫中，在第八次给予 MPTP 后观察到类似的震颤，即使在未给予中缝背核的猫中也是如此。结论：即使在猫身上，也有可能产生类似于帕金森氏震颤的静止性震颤。可以得出结论，中缝核5-羟色胺系统和黑核多巴胺系统的损伤可能与帕金森震颤的机制有关。