Abstract
In contrast to mammalian adults, myelination in teleosts occurs throughout their lifespan and most of the progenitor cells are originated in the cerebellum. To understand the role that thyroid hormones (THs) play in juvenile cerebellar myelination in teleosts, we identified and localised the expression of genes involved in TH signalling (mct8, oatp1c1, dio2, dio3, thraa and l-thrb1) and analysed the effects of the two bioactive THs, T2 and T3, upon their regulation, as well as upon some structural components of the myelination process. Ex vivo approaches using organotypic cerebellar cultures followed by FISH and qPCR showed gene-specific localisation and regulation of TH signalling genes in the cerebellar nuclei. In vivo approaches using methimazole (MMI)-treated juvenile tilapias replaced with low doses of T3 and T2 showed by immunofluorescence that myelin fibres in the cerebellum are more abundant in the granular layer and that their visible size is reduced after MMI treatment but partially restored with TH replacement, suggesting that low doses of TH promote the re-myelination process in an altered condition. Together, our data support the idea that T2 and T3 promote myelination via different pathways and prompt T2 as a target for further analysis as a promising therapy for hypomyelination.
Highlights
To investigate if the three sets of genes involved in thyroid hormones (THs) action were expressed in the teleost cerebellum, as well as their possible regulation by THs, organotypic cerebellum cultures were exposed to different T2 and T3 concentrations, and reverse transcribed (RT)-qPCR analysis was used to quantify gene expression
TH actions and effects during neurodevelopment are well known and conserved across different vertebrates; little is known about their role in adult neurogenesis[22]
A substantial percentage of mitotic cells within the proliferative zone are located in the cerebellum, and this proportion is maintained beyond early development and throughout adult life[16,18]
Summary
Cerebellum[18,19]. Teleost continuous neurogenesis is explained by the persistence of the radial glia beyond early development[20]. During the juvenile stage, a window of action for TH agonists and antagonists has been shown to compromise cerebellar physiological processes (connections, dendritic arborization, persistent myelination, among others)[15]. The juvenile teleost cerebellum is an excellent model system to study TH actions upon myelination processes in non-developing vertebrates[20]. The mechanisms of TH regulation in the cerebellum remain unclear; we recently described two different gene populations associated with myelination and development regulated either by T2 or T3 in juvenile tilapia cerebellum, suggesting that these two hormones could elicit specific and non-redundant functions in this tissue[9]. As an initial approach to understand the role that THs play in juvenile cerebellar myelination in teleosts, in the present work we identified and localised the expression of genes involved in TH signalling and analysed the effects of the two bioactive THs, T2 and T3, upon their regulation. We explored the regulatory effect of these hormones on some structural components of the myelination process
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