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Thyroid Hormone Disruption Effects Lamination of the Neocortex but not the Cerebellum in a Model of Developmental Hypothyroidism and Hypothyroxinemia
Van Dine, S., M. Gilbert, AND R. Ramos. Thyroid Hormone Disruption Effects Lamination of the Neocortex but not the Cerebellum in a Model of Developmental Hypothyroidism and Hypothyroxinemia. Presented at Osteopathic Medical Conference and Exposition (OMED), Seattle, WA, October 25 - 29, 2014.
This abstract will be presented at the Osteopathic Medical Conference and Exposition (OMED) 2014, October 25-29, 2014, Seattle, WA, National Student Osteopathic Medical Association Research Poster Presentation
Introduction: Research on neurodevelopmental changes resulting from thyroid hormone (TH) disruption has important basic and clinical implications. We previously demonstrated, in a rodent model, that developmental hypothyroidism or hypothyroxinemia can cause the formation of subcortical band heterotopia (SBH; Gilbert et al. 2014), indicating that TH plays a role in neuronal migration during corticogenesis. However, the effects of TH disruption on cerebellar development and lamination have not been evaluated in this model. Hypothesis: Hypothyroidism and hypothyroxinemia results in neuronal migration defects and altered lamination of the cerebellum by affecting the migration of granule cells. In light of our recent findings that ~30% of control rats exhibit spontaneous molecular layer heterotopia (MLH) of the cerebellar vermis (Van Dine et al. 2013), we hypothesize that TH disruption will increase the prevalence and size of MLH. Methods: Pregnant Long-Evans rats were administered propylthiouracil (PTU) via the drinking water from gestational day 6 until postnatal day 21. Brains from adult offspring from 0% (n=15), 0.0001% (n=13), and 0.00 1% (n=15) PTU dose groups were harvested for Nissl staining and immunocytochemistry to visualize cell-types and lamination defect in the cerebellum and neocortex. Digital photomicrographs of cerebellar and neocortical sections were used for analysis. Chi-square analyses were used to compare effects across groups alpha set at (p≤0.05). Results: All doses of PTU tested produced a SBH in the cortex which increased in size with increasing dose level and were correlated with reduced serum T4. In contrast, no cerebellar lamination defects were observed at any dose, although the presence of MLH was observed in all groups. Chi-square analyses indicated no significant dose-dependent increase in prevalence or size of cerebellar MLH. Conclusions: Our results indicate that although hypothyroidism and hypothyroxinemia produce robust and permanent neocortical malformations, cerebellar lamination and foliation appear intact when assessed in adult tissue. However, examination of neonatal and juvenile cerebellar tissue from treated rats may reveal migration delays as has been previously reported. Together with our previous findings, these data indicate that mild TH disruption can affect brain development, but these effects are both timing- and region-specific.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION