Citation:

Nance, J., R. Switzer III, A. Tennant, A. Johnstone, AND M. Gilbert. Does developmental hypothyroidism produce lasting effects on adult neurogenesis? Presented at Society of Toxicology meeting, March 10 - 14, 2013.

Impact/Purpose:

This abstract will be presented at the Society of Toxicology meeting March 10-14, 2013, San Antonio, TX

Description:

The subgranular zone of the dentate gyrus (DO) of the adult hippocampus generates new neurons throughout life. Thyroid hormones (TH) are essential for brain development, but impaired neurogenesis with adult hypothyroidism has also been reported. We investigated the role of milder degrees of TH disruption on adult neurogenesis following hypothyroidism induced during development, in adulthood, or both. Pregnant dams were administered the TH synthesis inhibitor, propylthiouracil (PTU, 0 or 3ppm in drinking water) from gestational day 6 and pups were weaned to control water on postnatal day (PN)2 I. On PN6O, offspring from control or PTU dams were either re-exposed to PTU (3ppm) for I month or maintained on control. Bromodeoxyuridine (BrdU 50 mg/kg, ip, twice daily) was administered to all animals on the last 5 days of the re-exposure period, and animals sacrificed 28 d later. Animals were perfused intracardially, the brains were removed, embedded in a MultiBrain (NSA) array and freeze sectioned. Every 8th section throughout the hippocampus was stained with an antibody against BrdU to mark actively dividing cells. The volume of the DO and the number of BrdUpositive cells were assessed from images captured on a Nikon microscope (200X) and Nikon Elements software. Preliminary findings indicate that developmental exposure to PTU produced a persistent reduction in the volume of the adult DO. BrdU cell counts were reduced similarly in all P11J-exposed groups. These data suggest that moderate levels of hypothyroidism decrease survival on newly generated cells in the adult brain and that transient developmental hypothyroidism leadsto persistent decreases in DO volume and cell survival. The degree to which these findings are determined by reductions in cell proliferation is currently under investigation. As neurogenesis in the adult recapitulates developmental processes of proliferation, differentiation, and migration, study of this neurogenic niche in the adult may provide a simpler means to assess the consequences of TH insufficiency on neurodevelopment. (Does not reflect EPA policy).

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