Thyroid hormone treated astrocytes induce maturation of cerebral cortical neurons through modulation of proteoglycan levels

Proper brain neuronal circuitry formation and synapse development is dependent on specific cues, either genetic or epigenetic, provided by the surrounding neural environment. Within the sesignals, thyroid hormones (T3 and T4) play crucial role in several steps of brain morphogenesis including proliferation of progenitor cells, neuronal differentiation, maturation, migration, and synapse formation. the lack of thyroid hormones during childhood is associated with several impair neuronal connections, cognitive deficits, and mental disorders. Many of the thyroid hormones effects are mediated by astrocytes, although the mechanisms underlying these events are still unknown. in this work, we investigated the effect of 3,5,3'-triiodothyronine-treated (T3-treated) astrocytes on cerebral cortex neuronal differentiation. Culture of neural progenitors from embryonic cerebral cortex mice onto T3-treated astrocyte monolayers yielded an increment in neuronal population, followed by enhancement of neuronal maturation, arborization and neurite outgrowth. in addition, real time PCR assays revealed an increase in the levels of the heparan sulfate proteoglycans, Glypican 1(GPC-1) and Syndecans 3 e 4 (SDC-3 e SDC-4), followed by a decrease in the levels of the chondroitin sulfate proteoglycan, Versican. Disruption of glycosaminoglycan chains by chondroitinase AC or heparanase III completely abolished the effects of T3-treated astrocytes on neuronal morphogenesis. Our work provides evidence that astrocytes are key mediators of T3 actions on cerebral cortex neuronal development and identified potential molecules and pathways involved in neurite extension; which might eventually contribute to a better understanding of axonal regeneration, synapse formation, and neuronal circuitry recover.Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Conselho Nacional para o Desenvolvimento Cientifico e TecnologicoCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21949590 Rio de Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Inst Bioquim Med, BR-21949590 Rio de Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, BR-21949590 Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilWeb of Scienc

MicroRNA in Acromegaly: Involvement in the Pathogenesis and in the Response to First-Generation Somatostatin Receptor Ligands

Acromegaly is a chronic and systemic disease due to excessive growth hormone and insulin-like growth factor type I caused, in the vast majority of cases, by a GH-secreting pituitary adenoma. About 40% of these tumors have somatic mutations in the stimulatory G protein alpha-subunit 1 gene. The pathogenesis of the remaining tumors, however, is still not fully comprehended. Surgery is the first-line therapy for these tumors, and first-generation somatostatin receptor ligands (fg-SRL) are the most prescribed medications in patients who are not cured by surgery. MicroRNAs are small, non-coding RNAs that control the translation of many mRNAs, and are involved in the post-transcriptional regulation of gene expression. Differentially expressed miRNAs can explain differences in the pathogenesis of acromegaly and tumor resistance. In this review, we focus on the most validated miRNAs, which are mainly involved in acromegaly’s tumorigenesis and fg-SRL resistance, as well as in circulating miRNAs in acromegaly