Institute of Neurobiology, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Duesseldorf, Duesseldorf, Germany.
Eur J Neurosci. 2021 Sep;54(5):5649-5672. doi: 10.1111/ejn.14780. Epub 2020 May 30.
In the rodent forebrain, the majority of astrocytes are generated during the early postnatal phase. Following differentiation, astrocytes undergo maturation which accompanies the development of the neuronal network. Neonate astrocytes exhibit a distinct morphology and domain size which differs to their mature counterparts. Moreover, many of the plasma membrane proteins prototypical for fully developed astrocytes are only expressed at low levels at neonatal stages. These include connexins and Kir4.1, which define the low membrane resistance and highly negative membrane potential of mature astrocytes. Newborn astrocytes moreover express only low amounts of GLT-1, a glutamate transporter critical later in development. Furthermore, they show specific differences in the properties and spatio-temporal pattern of intracellular calcium signals, resulting from differences in their repertoire of receptors and signalling pathways. Therefore, roles fulfilled by mature astrocytes, including ion and transmitter homeostasis, are underdeveloped in the young brain. Similarly, astrocytic ion signalling in response to neuronal activity, a process central to neuron-glia interaction, differs between the neonate and mature brain. This review describes the unique functional properties of astrocytes in the first weeks after birth and compares them to later stages of development. We conclude that with an immature neuronal network and wider extracellular space, astrocytic support might not be as demanding and critical compared to the mature brain. The delayed differentiation and maturation of astrocytes in the first postnatal weeks might thus reflect a reduced need for active, energy-consuming regulation of the extracellular space and a less tight control of glial feedback onto synaptic transmission.
在啮齿动物的前脑中,大多数星形胶质细胞是在出生后的早期阶段产生的。分化后,星形胶质细胞经历成熟过程,伴随着神经元网络的发育。新生星形胶质细胞表现出独特的形态和域大小,与成熟的星形胶质细胞不同。此外,许多成熟星形胶质细胞特有的质膜蛋白在新生阶段的表达水平较低。这些蛋白包括连接蛋白和 Kir4.1,它们定义了成熟星形胶质细胞的低膜电阻和高度负膜电位。新生星形胶质细胞此外只表达低水平的 GLT-1,这是一种谷氨酸转运体,在发育后期至关重要。此外,它们在细胞内钙信号的特性和时空模式上表现出特定的差异,这是由于它们的受体和信号通路谱的差异。因此,成熟星形胶质细胞所发挥的作用,包括离子和递质平衡,在年轻的大脑中发育不全。同样,星形胶质细胞对神经元活动的离子信号反应,这是神经元-胶质相互作用的核心过程,在新生和成熟大脑之间存在差异。这篇综述描述了出生后第一周星形胶质细胞的独特功能特性,并将其与发育的后期阶段进行了比较。我们得出结论,由于不成熟的神经元网络和更宽的细胞外空间,与成熟大脑相比,星形胶质细胞的支持可能不那么需要和关键。因此,出生后第一周星形胶质细胞的分化和成熟延迟可能反映了对细胞外空间进行积极、耗能调节的需求减少,以及对突触传递的胶质反馈的控制不那么严格。