Miwa Hideto, Kubo Tomomi, Suzuki Ai, Kihira Tameko, Kondo Tomoyoshi
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-City, Wakayama 641-8510, Japan.
Brain Res. 2006 Jan 12;1068(1):94-101. doi: 10.1016/j.brainres.2005.11.036. Epub 2006 Jan 10.
The rodent model of harmaline-induced tremor has been widely used for experimental analysis of tremor. Activation of the olivocerebellar system plays a key role in tremor-generating mechanisms. One undetermined problem is whether there are species-specific differences in effects of harmaline. The present study investigated effects of harmaline on olivocerebellar systems of mice and rats. Systemic administration of harmaline, but not vehicle, produced generalized, high-frequency tremors in both types of rodents. Immunohistochemical studies revealed significant degeneration of Purkinje cells that was associated with activated microgliosis in the cerebellar cortex, following administration of harmaline in rats but not in mice. However, in mice but not rats, microgliosis was induced following administration of harmaline in the inferior olivary nucleus (ION), particularly in its caudal and medial subdivisions. Numbers of neurons in the mouse ION did not decrease, suggesting the possibility that microgliosis in ION might not be a simple neurotoxic effect. Presumably, differences in sensitivity of Purkinje cells between rats and mice may be related to differences in functional alterations in their respective olivocerebellar systems induced by harmaline. Recognition of these species-specific differences in the response of the olivocerebellar system to harmaline is an important consideration for experimental analysis of the rodent model of tremors.
Harmaline诱导震颤的啮齿动物模型已被广泛用于震颤的实验分析。橄榄小脑系统的激活在震颤产生机制中起关键作用。一个尚未确定的问题是harmaline的作用是否存在物种特异性差异。本研究调查了harmaline对小鼠和大鼠橄榄小脑系统的影响。全身性给予harmaline而非赋形剂，在两种啮齿动物中均产生了全身性高频震颤。免疫组织化学研究显示，在大鼠而非小鼠中给予harmaline后，小脑皮质浦肯野细胞出现明显退化，并伴有小胶质细胞激活。然而，在小鼠而非大鼠中，给予harmaline后下橄榄核（ION）诱导了小胶质细胞激活，特别是在其尾侧和内侧亚区。小鼠ION中的神经元数量没有减少，这表明ION中小胶质细胞激活可能不是一种简单的神经毒性作用。推测，大鼠和小鼠浦肯野细胞敏感性的差异可能与harmaline诱导的各自橄榄小脑系统功能改变的差异有关。认识到橄榄小脑系统对harmaline反应的这些物种特异性差异是震颤啮齿动物模型实验分析的一个重要考虑因素。
