Purkinje cells and Bergmann glia are primary targets of the TRα1 thyroid hormone receptor during mouse cerebellum postnatal development

Fauquier, Teddy; Chatonnet, Fabrice; Picou, Frédéric; Richard, Sabine; Fossat, Nicolas; Aguilera, Nadine S.; Lamonerie, Thomas; Flamant, Frédéric

doi:10.1242/dev.103226

Cited by 79 publications

(58 citation statements)

References 58 publications

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“…7). Similar non-autonomous effects on GC maturation were also demonstrated in mice expressing a dominant-negative TH receptor in PCs (Fauquier et al 2014, Yu et al 2015.…”

Section: Mct8-deficient Pcs Disrupt Gc Precursor Proliferation and Posupporting

confidence: 65%

“…Correspondingly, the TH receptor α gene (THRA) is strongly expressed in chicken embryos at these early stages of PC development (Vancamp P, Delbaere J & Darras VM, unpublished observations), suggesting that impaired T 3 -mediated transcriptional action could underlie the MCT8-deficient phenotype. The fact that the effects of targeted MCT8 deficiency in the chicken embryo are similar to those seen in mice expressing a dominant-negative TH receptor in PCs (Fauquier et al 2014, Yu et al 2015 clearly stresses the importance of MCT8 at the neuronal level independent of its role in TH transport across brain barriers.…”

Section: :2mentioning

confidence: 91%

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MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development

Delbaere

Vancamp

Herck

et al. 2017

Journal of Endocrinology

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Inactivating mutations in the human SLC16A2 gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) result in the Allan-Herndon-Dudley syndrome accompanied by severe locomotor deficits. The underlying mechanisms of the associated cerebellar maldevelopment were studied using the chicken as a model. Electroporation of an MCT8-RNAi vector into the cerebellar anlage of a 3-dayold embryo allowed knockdown of MCT8 in Purkinje cell precursors. This resulted in the downregulation of the thyroid hormone-responsive gene RORα and the Purkinje cell-specific differentiation marker LHX1/5 at day 6. MCT8 knockdown also results in a smaller and less complex dendritic tree at day 18 suggesting a pivotal role of MCT8 for cell-autonomous Purkinje cell maturation. Early administration of the thyroid hormone analogue 3,5,3′-triiodothyroacetic acid partially rescued early Purkinje cell differentiation. MCT8-deficient Purkinje cells also induced non-autonomous effects as they led to a reduced granule cell precursor proliferation, a thinner external germinal layer and a loss of PAX6 expression. By contrast, at day 18, the external germinal layer thickness was increased, with an increase in presence of Axonin-1-positive post-mitotic granule cells in the initial stage of radial migration. The concomitant accumulation of presumptive migrating granule cells in the molecular layer, suggests that inward radial migration to the internal granular layer is stalled. In conclusion, early MCT8 deficiency in Purkinje cells results in both cell-autonomous and non-autonomous effects on cerebellar development and indicates that MCT8 expression is essential from very early stages of development, providing a novel insight into the ontogenesis of the Allan-HerndonDudley syndrome.

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“…7). Similar non-autonomous effects on GC maturation were also demonstrated in mice expressing a dominant-negative TH receptor in PCs (Fauquier et al 2014, Yu et al 2015.…”

Section: Mct8-deficient Pcs Disrupt Gc Precursor Proliferation and Posupporting

confidence: 65%

Section: :2mentioning

confidence: 91%

MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development

Delbaere

Vancamp

Herck

et al. 2017

Journal of Endocrinology

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“…The observation that ntC values in Gliacultures superseded those measured in ntC Glia+ suggests that the glia plays a role in the regulation of transcription, regardless of the type of receptor examined; even when cells were only treated with BPA alone, consequential decrease in TR transcription was more evident if the glia was present in the culture. While these observations are in concordance with previous results (Yamaguchi et al, 2006;Fauquier et al, 2014), our data also show that the effects of BPA on TR transcription are multifactorial and, in addition, differ depending on the presence or the absence of glia.…”

Section: Receptor Mrna Levelssupporting

confidence: 94%

Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture

Somogyi

Horváth

Tóth

et al. 2016

Acta Veterinaria Hungarica

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Thyroid hormones (THs) and oestrogens are crucial in the regulation of cerebellar development. TH receptors (TRs) mediate these hormone effects and are regulated by both hormone families. We reported earlier that THs and oestradiol (E 2 ) determine TR levels in cerebellar cell culture. Here we demonstrate the effects of low concentrations (10 -10 M) of the endocrine disruptor (ED) bisphenol A (BPA) on the hormonal (THs, E 2 ) regulation of TRα,β in rat cerebellar cell culture. Primary cerebellar cell cultures, glia-containing and glia-destroyed, were treated with BPA or a combination of BPA and E 2 and/or THs. Oestrogen receptor and TH receptor mRNA and protein levels were determined by real-time qPCR and Western blot techniques. The results show that BPA alone decreases, while BPA in combination with THs and/or E 2 increases TR mRNA expression. In contrast, BPA alone increased receptor protein expressions, but did not further increase them in combination with THs and/or E 2 . The modulatory effects of BPA were mediated by the glia; however, the degree of changes also depended on the specific hormone ligand used. The results signify the importance of the regulatory mechanisms interposed between transcription and translation and raise the possibility that BPA could act to influence nuclear hormone receptor levels independently of ligand-receptor interaction.Key words: Endocrine disruptors, thyroid receptor, transcription, translation, bisphenol A, rat cerebellum Thyroid hormones (THs) and oestrogens (mostly 17β-oestradiol, E 2 ) play critical roles in the regulation of central nervous system (CNS) development, in-* Corresponding author; Zsarnovszky.Attila@mkk.szie.hu; Phone: 0036 (28) 522-062/1620 (office); 0036 (30) 665-3717 (mobile); Fax: 0036 (28) 522-062

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“…Thyroid hormones are extremely important for neural migration in cortex, hippocampus and cerebellum. Moreover, thyroid hormone is involved in the early phases of cellular migration from external germinal layer to internal germinal layer, causing delay in the migration of granular cells (Fauquier, 2014).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

Bhroz¹,

Parivar²,

Amiri³

et al. 2017

JMBR

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Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism. Materials and Methods:In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

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Purkinje cells and Bergmann glia are primary targets of the TRα1 thyroid hormone receptor during mouse cerebellum postnatal development

Cited by 79 publications

References 58 publications

MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development

MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar development

Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture

Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

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