Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil.
Front Cell Neurosci. 2013 Aug 12;7:125. doi: 10.3389/fncel.2013.00125. eCollection 2013.
Proper brain neuronal circuitry formation and synapse development is dependent on specific cues, either genetic or epigenetic, provided by the surrounding neural environment. Within these signals, 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.
适当的脑神经元回路形成和突触发育依赖于周围神经环境提供的特定线索，这些线索可以是遗传的也可以是表观遗传的。在这些信号中，甲状腺激素（T3 和 T4）在大脑形态发生的几个步骤中发挥关键作用，包括祖细胞的增殖、神经元分化、成熟、迁移和突触形成。儿童时期缺乏甲状腺激素与多种神经元连接受损、认知缺陷和精神障碍有关。甲状腺激素的许多作用是通过星形胶质细胞介导的，尽管这些事件的机制尚不清楚。在这项工作中，我们研究了 3,5,3'-三碘甲状腺原氨酸处理（T3 处理）星形胶质细胞对大脑皮层神经元分化的影响。将来自胚胎大脑皮层的神经前体细胞培养在 T3 处理的星形胶质细胞单层上，会导致神经元群体增加，随后增强神经元成熟、分支和轴突生长。此外，实时 PCR 检测显示硫酸乙酰肝素蛋白聚糖、Glypican 1（GPC-1）和 Syndecans 3 和 4（SDC-3 和 SDC-4）的水平增加，随后软骨素硫酸蛋白聚糖 Versican 的水平降低。硫酸乙酰肝素酶 III 或软骨素酶 AC 破坏糖胺聚糖链完全消除了 T3 处理星形胶质细胞对大脑皮层神经元形态发生的影响。我们的工作提供了证据表明星形胶质细胞是 T3 对大脑皮层神经元发育作用的关键介质，并确定了参与轴突延伸的潜在分子和途径；这可能最终有助于更好地理解轴突再生、突触形成和神经元回路恢复。
