Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors

Izuki Amano, Yusuke Takatsuru, Syutaro Toya, Asahi Haijima, Toshiharu Iwasaki, Helmut Grasberger, Samuel Refetoff, Noriyuki Koibuchi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Thyroid hormone (TH) plays a key role in the developing brain, including the cerebellum. TH deficiency induces organizational changes of the cerebellum, causing cerebellar ataxia. However, the mechanisms causing these abnormalities are poorly understood. Various animal models have been used to study the mechanism. Lacking dual oxidase (DUOX) and its maturation factor (DUOXA) are major inducers of congenital hypothyroidism. Thus, this study examined the organizational changes of the cerebellum using knockout mice of the Duoxa gene (Duoxa-/-). Methods: The morphological, behavioral, and electrophysiological changes were analyzed in wild type (Wt) and Duoxa-deficient (Duoxa-/-) mice from postnatal day (P) 10 to P30. To detect the changes in the expression levels of presynaptic proteins, Western blot analysis was performed. Results: The proliferation and migration of granule cells was delayed after P15 in Duoxa-/- mice. However, these changes disappeared by P25. Although the cerebellar structure of Duoxa-/- mice was not significantly different from that of Wt mice at P25, motor coordination was impaired. It was also found that the amplitude of paired-pulse facilitation at parallel fiber-Purkinje cell synapses decreased in Duoxa-/- mice, particularly at P15. There were no differences between expression levels of presynaptic proteins regulating neurotransmitter release at P25. Conclusions: These results indicate that the anatomical catch-up growth of the cerebellum did not normalize its function because of the disturbance of neuronal circuits by the combined effect of hypothyroidism and functional disruption of the DUOX/DUOXA complex.

Original languageEnglish
Pages (from-to)741-752
Number of pages12
JournalThyroid
Volume26
Issue number5
DOIs
Publication statusPublished - 2016 May 1
Externally publishedYes

Fingerprint

Oxidoreductases
Cerebellum
Organizational Innovation
Thyroid Hormones
Genes
Congenital Hypothyroidism
Cerebellar Ataxia
Purkinje Cells
Hypothyroidism
Knockout Mice
Synapses
Cell Movement
Neurotransmitter Agents
Proteins
Animal Models
Western Blotting
Brain
Growth

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Amano, I., Takatsuru, Y., Toya, S., Haijima, A., Iwasaki, T., Grasberger, H., ... Koibuchi, N. (2016). Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors. Thyroid, 26(5), 741-752. https://doi.org/10.1089/thy.2015.0034

Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors. / Amano, Izuki; Takatsuru, Yusuke; Toya, Syutaro; Haijima, Asahi; Iwasaki, Toshiharu; Grasberger, Helmut; Refetoff, Samuel; Koibuchi, Noriyuki.

In: Thyroid, Vol. 26, No. 5, 01.05.2016, p. 741-752.

Research output: Contribution to journalArticle

Amano, I, Takatsuru, Y, Toya, S, Haijima, A, Iwasaki, T, Grasberger, H, Refetoff, S & Koibuchi, N 2016, 'Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors', Thyroid, vol. 26, no. 5, pp. 741-752. https://doi.org/10.1089/thy.2015.0034
Amano I, Takatsuru Y, Toya S, Haijima A, Iwasaki T, Grasberger H et al. Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors. Thyroid. 2016 May 1;26(5):741-752. https://doi.org/10.1089/thy.2015.0034
Amano, Izuki ; Takatsuru, Yusuke ; Toya, Syutaro ; Haijima, Asahi ; Iwasaki, Toshiharu ; Grasberger, Helmut ; Refetoff, Samuel ; Koibuchi, Noriyuki. / Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors. In: Thyroid. 2016 ; Vol. 26, No. 5. pp. 741-752.
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