Effects of Mild Perinatal Hypothyroidism on Cognitive Function of Adult Male Offspring

Izuki Amano, Yusuke Takatsuru, Miski Aghnia Khairinisa, Michifumi Kokubo, Asahi Haijima, Noriyuki Koibuchi

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Abstract

Mild perinatal hypothyroidism may result from inadequate iodine intake, insufficient treatment of congenital hypothyroidism, or exposure to endocrine-disrupting chemicals. Because thyroid hormones are critical for brain development, severe hypothyroidism that is untreated in infancy causes irreversible cretinism. Milder hypothyroidism may also affect cognitive development; however, the effects of mild and/or moderate hypothyroidism on brain development are not fully understood. In this study, we examined the behavior of adult male mice rendered mildly hypothyroid during the perinatal period using low-dose propylthiouracil (PTU). PTU was administered through drinking water (5 or 50 ppm) from gestational day 14 to postnatal day 21. Cognitive performance, studied by an object in-location test (OLT), was impaired in PTU-treated mice at postnatal week 8. These results suggest that, although the hypothyroidism was mild, it partially impaired cognitive function. We next measured the concentration of neurotransmitters (glutamate, γ-aminobutyric acid, and glycine) in the hippocampus using in vivo microdialysis during OLT. The concentrations of neurotransmitters, particularly glutamate and glycine, decreased in PTU-treated mice. The expression levels of N-methyl-d-aspartate receptor subunits, which are profound regulators of glutamate neurotransmission and memory function, also were decreased in PTU-treated mice. These data indicate that mild perinatal hypothyroidism causes cognitive disorders in adult offspring. Such disorders may be partially induced secondary to decreased concentrations of neurotransmitters and receptor expression.

Original languageEnglish
Pages (from-to)1910-1921
Number of pages12
JournalEndocrinology
Volume159
Issue number4
DOIs
Publication statusPublished - 2018 Apr 1
Externally publishedYes

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ASJC Scopus subject areas

  • Endocrinology

Cite this

Amano, I., Takatsuru, Y., Khairinisa, M. A., Kokubo, M., Haijima, A., & Koibuchi, N. (2018). Effects of Mild Perinatal Hypothyroidism on Cognitive Function of Adult Male Offspring. Endocrinology, 159(4), 1910-1921. https://doi.org/10.1210/en.2017-03125