Abstract: Developmental hypothyroidism causes brain retardation due to impairment of neuronal migration and oligodendroglial myelination. Brominated flame retardants (BFRs), potential environmental pollutants to cause bioaccumulation, usually exert low or no toxicity in conventional toxicity studies, but some of them are known to induce mild hypothyroidism. To search for target genes responsible for possible brain retardation due to developmental exposure to BFRs, we performed a global gene expression profiling specific to the cerebral white matter of rat pups exposed to decebromodiphenyl ether (DBDE) during development. Dams were given DBDE at 10, 100, or 1000 ppm in diet during the period from gestation day 10 to postnatal day 21 (weaning). As a positive control for hypothyroidism, methimazole (MMI) at 200 ppm or propylthiouracil (PTU) at 3 or 12 ppm was given via drinking water. At weaning, bilateral cerebral white matter and corpus callosum (CC) were selectively microdissected from male pups and subjected to microarray analysis. As a result, 10% of genes showing altered expression by DBDE were identical to those induced by anti-thyroid agents (MMI and PTU) including glial cell differentiation, axon guidance, myelination, or cellular migration. Also, DBDE-alone induced expression alteration of genes related to similar functions as with anti-thyroid agents. At 11 weeks of age, offspring were subjected to brain morphometry regarding white matter components. As a result, as well as anti-thyroid agents, DBDE reduced the CC area and the density of CNPase-positive oligodendrocytes suggestive of reduced white matter development. Results thus suggest that glial development-related genes obtained here with DBDE may be linked to or independent of developmental hypothyroidism that is shown here for the first time with DBDE as white matter hypoplasia.
Publication Year: 2009
Publication Date: 2009-05-01
Language: en
Type: article
Indexed In: ['crossref']
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