Neuroscience 2005 Abstract
| Presentation Number: | 480.23 |
|---|---|
| Abstract Title: | Developmental hypothyroidism induces a cortical malformation populated by neurons born late in gestation. |
| Authors: |
Gilbert, M. E.*1
; Schon, J. P.2
; Phani, S.2
; Goodman, J. H.2
1Neurotoxicology, US EPA, RTP, NC 2NY, MD B105-05, 27711, |
| Primary Theme and Topics |
Development - Neurogenesis and Gliogenesis -- Cell migration |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Developmental Disorders<br />-- Acquired |
| Session: |
480. Cell Migration Poster |
| Presentation Time: | Monday, November 14, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # B27 |
| Keywords: | HORMONE, HPA AXIS, CALLOSUM, MIGRATION |
We previously described an abnormal cluster of neurons, a heterotopia, located in the corpus callosum in rat pups born to dams exposed to the goitrogen, propylthiouracil (PTU, Goodman et al., SfN 2004). In this study we determined 1) whether the formation of the heterotopia was unique to hypothyroidism induced by PTU and 2) the birth date of the cells contained within the heterotopia. Pregnant LE rats were exposed to methimazole (MMI, 200 ppm) or PTU (10 ppm) in drinking water from gestational day (GD) 6 to postnatal day (PN) 30. Offspring were perfused with 4% paraformaldehyde (PAF) on PN23 and PN86 and the brains prepared for histological analysis. Heterotopias were present in all pups examined from PTU and MMI dams. The bulk of the cells comprising the heterotopia were of a neuronal phenotype. To determine the birth date of these cells pregnant dams were exposed to 0, 1, 3 or 10 ppm PTU from GD6-PN30. Dams from each dose group also received 50 mg/kg of bromodeoxyuracil (BrdU), ip, once daily from GD 14-16 or GD 17-19. Pups were sacrificed on PN4, 10, 23 and 86, brains were fixed in 4% PAF, and tissue processed for BrdU immunostaining. A heterotopia was never observed in controls, but was present in all animals exposed to 3 and 10 ppm, and 50% of animals from the 1 ppm dose group. Many BrdU-positive cells were present in the heterotopia of offspring of dams injected between GD17-19 but were absent in the heterotopia of offspring of dams injected on GD14-16. These results confirm that this cortical malformation is induced by thyroid hormone insufficiency. Cells within the heterotopia are born late in gestation and may have been destined for cortex or hippocampus. We postulate that some developmental disorders of childhood origin stemming from altered cell migration may derive from early thyroid hormone insufficiency. Does not reflect EPA policy.
Supported by US EPA
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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