Thyroid hormone insufficiency alters the expression of psychiatric disorder-related molecules in the hypothyroid mouse brain during the early postnatal period

Katsuya Uchida,Kentaro Hasuoka,Toshimitsu Fuse,Kenichi Kobayashi,Keiichi Itoi,Norihiro Katayama,Takahiro Moriya,Mao Suzuki

doi:10.1038/s41598-021-86237-8

Abstract

The functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study. TH insufficiency showed a decrease in the expression of parvalbumin (PV) in the cortex and hippocampus of pups at postnatal day (PD) 14, while treatment with thyroxine from PD 0 to PD 14 ameliorated the PV loss. On the other hand, treatment with antithyroid agents in adulthood did not result in a decrease in the expression of PV in these areas. These results indicate the existence of a critical period of TH action during the early postnatal period. A decrease in MeCP2-positive neuronal nuclei was also observed in the cortical layers II–IV of the cerebral cortex. The brains were then stained with CUX1, a marker for cortical layers II–IV. In comparison with normal mice, CUX1 signals were decreased in the somatosensory cortex of the hypothyroid mice, and the total thickness of cortical layers II–IV of the mice was lower than that of normal mice. These results suggest that TH insufficiency during the perinatal period strongly and broadly affects neuronal development.

Highlights

The functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study
PV mRNA was broadly distributed in the cortical layers II–VI of the cerebral cortex of normal mice (Fig. 3A,B), TH insufficiency during E 17.5 to postnatal day (PD) 14 resulted in the loss of PV expression in these areas (Fig. 3D,E)
In both the cortex and hippocampus, quantitative PCR (qPCR) analysis indicated that the levels of PV mRNA expression were decreased by treatment with an antithyroid agent during the perinatal period, while the expression levels recovered upon exogenous T4 treatment from just after birth to PD 14 (Fig. 3G,H)

Summary

Introduction

The functional role of thyroid hormone (TH) in the cortex and hippocampus of mouse during neuronal development was investigated in this study. In comparison with normal mice, CUX1 signals were decreased in the somatosensory cortex of the hypothyroid mice, and the total thickness of cortical layers II–IV of the mice was lower than that of normal mice These results suggest that TH insufficiency during the perinatal period strongly and broadly affects neuronal development. We have reported that the number of PV-expressing neurons is low in the cerebral cortex of growth-retarded mice used as a mouse model of hypothyroidism. This phenomenon was ameliorated by treatment with tri-iodothyronine (T3) from PD 0 to PD 208. We report that the expression of psychiatric disorders-related molecules in the hypothyroid brain of mice is altered by TH insufficiency during the early postnatal period

Methods

Results

Conclusion