Deletion of Neuroligins from Astrocytes Does Not Detectably Alter Synapse Numbers or Astrocyte Cytoarchitecture by Maturity.

Samantha R Golf, Justin H Trotter, Jinzhao Wang, George Nakahara, Xiao Han, Marius Wernig, Thomas C Südhof
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Abstract

Astrocytes perform multifarious roles in the formation, regulation, and function of synapses in the brain, but the mechanisms involved are incompletely understood. Interestingly, astrocytes abundantly express neuroligins, postsynaptic adhesion molecules that function as synaptic organizers by binding to presynaptic neurexins. Here we examined the function of neuroligins in astrocytes with a rigorous genetic approach that uses the conditional deletion of all major neuroligins (Nlgn1-3) in astrocytes in vivo and complemented this approach by a genetic deletion of neuroligins in glia cells that are co-cultured with human neurons. Our results show that early postnatal deletion of neuroligins from astrocytes in vivo has no detectable effect on cortical or hippocampal synapses and does not alter the cytoarchitecture of astrocytes when evaluated in young adult mice. Moreover, deletion of astrocytic neuroligins in co-cultures of human neurons produced no detectable consequences for the formation and function of synapses. Thus, astrocytic neuroligins are unlikely to fundamentally shape synapse formation or astrocyte morphogenesis but likely perform other important roles that remain to be discovered.

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星形细胞神经胶质蛋白不是突触形成或正常星形细胞细胞结构所必需的。
星形胶质细胞在大脑突触的形成、调节和功能中发挥着多种作用,但其机制尚不清楚。有趣的是,星形胶质细胞大量表达神经胶质蛋白,这是一种与突触前神经元结合的突触后粘附分子。最近的一项开创性研究报告称,星形胶质细胞中神经胶质蛋白功能的丧失会损害兴奋性突触的形成和星形胶质细胞的形态发生。这项研究表明星形胶质细胞神经胶质蛋白具有关键的突触功能,但令人困惑的是,组成型神经胶质蛋白缺失不会减少兴奋性突触的数量。因此,我们在这里使用严格的条件遗传学方法检测了星形胶质细胞神经胶质蛋白的功能,其中星形胶质细胞中所有主要神经胶质蛋白(Nlgn1-3)都被缺失。我们的研究结果表明,出生后早期从星形胶质细胞中缺失神经胶质蛋白对皮层或海马突触没有影响,也不会改变星形胶质细胞的细胞结构。因此,星形胶质细胞神经胶质蛋白不太可能形成突触或星形胶质细胞发育,但可能在星形胶质细胞中发挥其他重要功能。
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