A histologically derived stereotaxic atlas and substance P immunohistochemistry in the brain of the least shrew ( Cryptotis parva) support its role as a model organism for behavioral and pharmacological research

Abstract

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.