ArticleThyroid : official journal of the American Thyroid Association2016
Aberrant Cerebellar Development in Mice Lacking Dual Oxidase Maturation Factors.
Article in Thyroid : official journal of the American Thyroid Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
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- Cross-species applicability of an adverse outcome pathway network for thyroid hormone system disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2023Review
- Thyroid hormone action during GABAergic neuron maturation: The quest for mechanisms.Frontiers in endocrinology · 2023Review
- Histone Deacetylase 3 Inhibitor Alleviates Cerebellar Defects in Perinatal Hypothyroid Mice by Stimulating Histone Acetylation and Transcription at Thyroid Hormone-Responsive Gene Loci.International journal of molecular sciences · 2022Article
- The Role of Thyroid Hormone in the Regulation of Cerebellar Development.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- Necroptosis mediated by receptor interacting protein kinase 3 as critical players in experimental congenital hypothyroidism related neuronal damage.Northern clinics of Istanbul · 2021Article
- Absence of Thyroid Hormone Induced Delayed Dendritic Arborization in Mouse Primary Hippocampal Neurons Through Insufficient Expression of Brain-Derived Neurotrophic Factor.Frontiers in endocrinology · 2021Article
- Early-life stress induces motor coordination dysfunction in adult mice.The journal of physiological sciences : JPS · 2018Article
- Article
- The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling.PLoS genetics · 2017Article
- Effects of Transforming Growth Factor Beta 1 in Cerebellar Development: Role in Synapse Formation.Frontiers in cellular neuroscience · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThyroid 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-/-).
methodsThe 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.
resultsThe 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.
conclusionsThese 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.
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