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Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats

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Abstract

The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague–Dawley, and Long–Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague–Dawley or Long–Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

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Acknowledgments

We thank Jeanne Quidore-Jermann and the staff of the New York Institute of Technology College of Osteopathic Medicine animal facility. This document has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Conflict of Interest

We, the authors of this manuscript, certify that we have no financial or other conflict of interest related to the data contained in the following publication.

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Authors and Affiliations

  1. Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Northern Boulevard, PO Box 8000, Old Westbury, NY, 11568, USA

    Raddy L. Ramos, Sarah E. Van Dine, Joerg R. Leheste & German Torres

  2. Toxicity Assessment Division, Neurotoxicology Branch, US Environmental Protection Agency, Research Triangle Park, Durham, NC, USA

    Mary E. Gilbert

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  1. Raddy L. Ramos
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  2. Sarah E. Van Dine
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Correspondence to Raddy L. Ramos.

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Ramos, R.L., Van Dine, S.E., Gilbert, M.E. et al. Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats. Cerebellum 14, 624–631 (2015). https://doi.org/10.1007/s12311-015-0657-9

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