Thyroid hormone participates in the regulation of neural stem cells and oligodendrocyte precursor cells in the central nervous system of adult rat

Abstract

Oligodendrocyte development and myelination are under thyroid hormone control. In this study we analysed the effects of chronic manipulation of thyroid status on the expression of a wide spectrum of oligodendrocyte precursor cells (OPCs) markers and myelin basic protein (MBP) in the subventricular zone (SVZ), olfactory bulb and optic nerve, and on neural stem cell (NSC) lineage in adult rats. Hypo- and hyperthyroidism were induced in male rats, by propyl-thio-uracil (PTU) and L-thyroxin (T4) treatment, respectively. Hypothyroidism increased and hyperthyroidism downregulated proliferation in the SVZ and olfactory bulb (Ki67 immunohistochemistry and Western blotting, bromodeoxyuridine uptake). Platelet-derived growth factor receptor alpha (PDGFalpha-R) and MBP mRNA levels decreased in the optic nerve of hypothyroid rats; the same also occurred at the level of MBP protein. Hyperthyroidism slightly upregulates selected markers such as NG2 in the olfactory bulb. The lineage of cells derived from primary cultures of NSC prepared from the forebrain of adult hypo- and hyperthyroid also differs from those derived from control animals. Although no difference of in vitro proliferation of NSCs was observed in the presence of epidermal growth factor, maturation of oligodendrocytes (defined by process number and length) was enhanced in hyperthyroidism, suggesting a more mature state than in control animals. This difference was even greater when compared with the hypothyroid group, the morphology of which suggested a delay in differentiation. These results indicate that thyroid hormone affects NSC and OPC proliferation and maturation also in adulthood.

Reduced glutamate in white matter of male neonates exposed to alcohol in utero: a 1H-magnetic resonance spectroscopy study

“…As previously mentioned, Glu, is required to signal processes of myelination; achieved by Glu’s activation of AMPA/kainate and NMDA receptors on immature oligodendrocytes (Karadottir and Attwell 2006), so too is effective thyroid hormone signalling required for the development and maturation of oligodendrocytes (Valcana et al 1975; Emery 2010; Fernandez et al 2004; Franco et al 2008; Mohacsik et al 2011). Oligodendrocytes sheath axons to ensure fast and efficient communication between brain regions, which is known to be attenuated in children and adolescents with FASD (Treit et al 2013; Spottiswoode et al 2011; Wozniak et al 2013).…”

Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

“…We show that Shh expression is rapidly regulated both in vivo and in vitro in response to thyroid hormone, accompanied by significant epigenetic histone modifications within upstream regions of the Shh gene. Both thyroid hormone and Shh have been independently demonstrated to regulate diverse aspects of central nervous system development, including effects on proliferation and maturation, and to retain a profound influence on the adult brain, modulating recruitment, survival, and differentiation of neuronal and oligodendrocytic progenitors (13, 14, 29, 31). Our results suggest that specific developmental and plasticity associated actions of thyroid hormone may be mediated by its control of the Shh pathway and motivate future experiments to determine the mechanistic contribution of Shh to the effects of thyroid hormone in both the developing and mature nervous system.…”

Dietary Exposure to 2,2′,4,4′-Tetrabromodiphenyl Ether (PBDE-47) Alters Thyroid Status and Thyroid Hormone–Regulated Gene Transcription in the Pituitary and Brain

“…Still, it is not known if BTEB regulates neurogenesis during this teleost life stage as it does during mammalian development. There is, however, accumulating evidence in mammals that THs regulate adult neurogenesis (Desouza et al 2005; Fernandez et al 2004; Tekumalla et al 2002). In adult rats, for instance, exogenous TH increases immunoreactivity for the cell proliferation marker Ki-67 in the subventricular zone of the brain (Giardino et al 2000).…”