Ray Andrew P, Darmani Nissar A
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 E 2nd Street, Pomona, CA 91766, USA.
Brain Res. 2007 Jul 2;1156:99-111. doi: 10.1016/j.brainres.2007.04.061. Epub 2007 May 4.
Chemotherapy is an effective treatment but difficult to tolerate due to side effects like vomiting. Studies on the etiology of chemotherapy-related emesis have implicated brainstem nuclei and the neurotransmitter substance P, among other substrates. Since rodents do not vomit, other species have been necessary as alternative models of chemotherapy-induced emesis. Of these, the least shrew (Cryptotis parva) has proven valuable due to its small size, hardiness, and close phylogenetic relationship with primates. However, very little neuroanatomical data on C. parva exist. We used histological and immunohistochemical techniques to provide neuroanatomical data to help validate C. parva as a model organism, especially for emesis research. Brains were sectioned and stained for Nissl substance or myelin, or immunofluorescently labeled for substance P. Sections were photographed, traced, and reconstructed with standardized zero points, and these data used to create a stereotaxic atlas. The brain of C. parva was similar to but smaller than other mammalian brains, with the cerebellum and hippocampus demonstrating the biggest differences. Differences appeared to be related to the small size of the brain and the metabolic compromises required of such a small mammal. Substance P-like immunoreactivity (SPL-IR) was semiquantitatively mapped, and correlated very well with SPL-IR observed in other species. Dense SPL-IR areas included the periaqueductal grey, trigeminal nuclei, dorsal raphe, and emesis-related brainstem nuclei including the area postrema and solitary tract nucleus. These data demonstrate that the anatomical differences between C. parva and other mammals will not preclude its use as a model organism.
化疗是一种有效的治疗方法,但由于呕吐等副作用而难以耐受。关于化疗相关性呕吐病因的研究表明,除其他底物外,脑干核团和神经递质P物质也与之有关。由于啮齿动物不会呕吐,因此需要其他物种作为化疗诱导呕吐的替代模型。其中,小麝鼩(Cryptotis parva)因其体型小、耐寒且与灵长类动物有密切的系统发育关系而被证明具有重要价值。然而,关于小麝鼩的神经解剖学数据非常少。我们使用组织学和免疫组织化学技术来提供神经解剖学数据,以帮助验证小麝鼩作为一种模式生物,特别是用于呕吐研究。将大脑切片并进行尼氏物质或髓磷脂染色,或对P物质进行免疫荧光标记。对切片进行拍照、追踪并使用标准化零点进行重建,这些数据用于创建一个立体定位图谱。小麝鼩的大脑与其他哺乳动物的大脑相似但较小,小脑和海马体表现出最大的差异。这些差异似乎与大脑的小尺寸以及这种小型哺乳动物所需的代谢妥协有关。对P物质样免疫反应性(SPL-IR)进行了半定量映射,并且与在其他物种中观察到的SPL-IR非常吻合。密集的SPL-IR区域包括导水管周围灰质、三叉神经核、中缝背核以及与呕吐相关的脑干核团,包括最后区和孤束核。这些数据表明,小麝鼩与其他哺乳动物之间的解剖学差异并不妨碍将其用作模式生物。