Perinatal methylmercury exposure perturbs the expression of Plp1 and Cnp splice variants in cerebellum of rat pups

Early life exposure to environmental chemicals can interfere with myelin formation in the developing brain, leading to neurological disorders. The Proteolipid Protein 1 (Plp1), Myelin Basic Protein (Mbp) and 2′,3′-Cyclic Nucleotide 3’Phosphodiesterase (Cnp) genes expressed in oligodendrocytes and involved in myelination processes can be useful biomarkers of potential developmental neurotoxicity. In an earlier study, the authors concluded that the reduction in the expression levels of Mbp splice variants in juvenile rat cerebellum following perinatal methylmercury (MeHg) exposure were compatible with an overall reduction of mature oligodendrocytes population. This observation prompted further analysis of the expression of Plp1 and Cnp in developing rat cerebellum to confirm and investigate the toxic effects of MeHg on vulnerable oligodendrocytes. Splice variants of Plp1 in human and of Cnp in mouse are curated in NCBI RefSeq database, but not for rat. Lack of annotation of splice variants can pose significant challenge for the reliable quantification of gene expression levels in toxicological studies. Therefore, a “comparative sequence analysis” approach, relying on annotated splice variants in human/mouse and on evolutionary conservation of intron-exon structures was applied, to identify additional splice variants of Plp1 and Cnp in rat. The authors then confirmed their identity by nucleotide sequencing and characterised their temporal expression patterns during brain development by RT-PCR. The measurement of total transcripts and individual splice variants of Plp1 and Cnp in the cerebellum of MeHg-exposed rat pups revealed a relatively similar level of reduction in their expression levels. The authors concluded that this study confirms that perinatal exposure to MeHg can impact oligodendrocytes in pups and that monitoring the expression of these oligodendrocyte-enriched genes can be useful to identify toxic chemicals affecting myelination.

Authors: Padhi BK, Rosales M, Pelletier G. ;Full Source: Neurotoxicology. 2015 May;48:223-30. doi: 10.1016/j.neuro.2015.04.006. Epub 2015 Apr 29. ;