• Ayako Shiraki, Hirotoshi Akane, Takumi Ohishi, Liyun Wang, Reiko Morita, Kazuhiko Suzuki, Kunitoshi Mitsumori, and Makoto Shibutani.
• Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
• Arch. Toxicol. 2012 Oct 1; 86 (10): 1559-69.

AbstractHypothyroidism affects neurogenesis. The present study was performed to clarify the sensitivity of neurogenesis-related cellular responses in the hippocampal dentate gyrus between developmental and adult-stage hypothyroidism. An exposure study of methimazole (MMI) as an anti-thyroid agent at 0, 50, 200 ppm in the drinking water was performed using pregnant rats from gestation day 10 to postnatal day (PND) 21 (developmental hypothyroidism) and adult male rats by setting an identical exposure period from PND 46 through to PND 77 (adult-stage hypothyroidism). Offspring with developmental hypothyroidism were killed at PND 21 or PND 77, and animals with adult-stage hypothyroidism were killed at PND 77. Proliferation and apoptosis were unchanged in the dentate subgranular zone by either developmental or adult-stage hypothyroidism. With regard to precursor granule cells, a sustained reduction of paired box 6-positive stem or early progenitor cells and a transient reduction of doublecortin-positive late-stage progenitor cells were observed after developmental hypothyroidism with MMI at 50 and 200 ppm. These cells were unchanged by adult-stage hypothyroidism. With regard to γ-aminobutyric acid (GABA) ergic interneuron subpopulations in the dentate hilus, the number of parvalbumin-positive cells was decreased and the number of calretinin-positive cells was increased after both developmental and adult-stage hypothyroidism with MMI at 50 and 200 ppm. Fluctuations in GABAergic interneuron numbers with developmental hypothyroidism continued through to PND 77 with 200 ppm MMI. Considering the roles of GABAergic interneuron subpopulations in neurogenesis and neuronal differentiation, subpopulation changes in GABAergic interneurons by hypothyroidism may be the signature of aberrant neurogenesis even at the adult stage.

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