Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.
Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.
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星形胶质细胞异常钙信号抑制人唐氏综合征干细胞模型神经元兴奋性。
DOI：
10.1016/j.celrep.2018.06.033
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发表时间：
2018-07-10
期刊：
影响因子：
8.8
通讯作者：
Tian L
中科院分区：
文献类型：
--
作者：
Mizuno GO;Wang Y;Shi G;Wang Y;Sun J;Papadopoulos S;Broussard GJ;Unger EK;Deng W;Weick J;Bhattacharyya A;Chen CY;Yu G;Looger LL;Tian L
唐氏综合症（DS）是一种导致认知障碍的遗传性疾病。与人类21号染色体额外拷贝（HSA21）相关的惊人效应使对退行性椎体滑移病理生理的机制理解复杂化。我们在从ds患者衍生的诱导多能干细胞（iPSCs）分化的完全重现的HSA21三体细胞模型中检测了神经元与星形胶质细胞的相互作用。通过钙显像与遗传学方法的结合，我们发现了DS星形胶质细胞的功能缺陷及其对神经元兴奋性的影响。与对照等基因星形胶质细胞相比，DS星形胶质细胞表现出更频繁的自发钙波动，这降低了共培养神经元的兴奋性。此外，通过阻断腺苷介导的信号传导，或通过敲低肌醇三磷酸（IP3）受体或HSA21上编码的钙结合蛋白S100B，通过化学方式消除星形细胞自发钙活性，可以挽救被抑制的神经元活性。我们的研究结果表明，DS改变星形胶质细胞的功能，从而扰乱神经元的兴奋性的机制。为了了解唐氏综合症（DS）如何影响神经网络，Mizuno等人利用DS患者来源的干细胞模型和钙成像研究了DS星形胶质细胞的功能缺陷及其对神经元兴奋性的影响。他们的研究表明，DS星形胶质细胞表现出更频繁的自发钙波动，这损害了神经元的兴奋性。
Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability. To understand how Down syndrome (DS) affects neural networks, Mizuno et al. used a DS-patient-derived stem cell model and calcium imaging to investigate the functional defects of DS astrocytes and their effects on neuronal excitability. Their study reveals that DS astroglia exhibited more frequent spontaneous calcium fluctuations, which impair neuronal excitability.
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影响因子：
3.7
作者：
Garcia O;Torres M;Helguera P;Coskun P;Busciglio J
通讯作者：
Busciglio J
DOI：
10.1111/j.1530-0277.2011.01722.x
发表时间：
2012-07
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Nam HW;McIver SR;Hinton DJ;Thakkar MM;Sari Y;Parkinson FE;Haydon PG;Choi DS
通讯作者：
Choi DS
影响因子：
4.2
作者：
Ballestin, Raul;Miguel Blasco-Ibanez, Jose;Varea, Emilio
通讯作者：
Varea, Emilio
DOI：
10.1073/pnas.0408483102
发表时间：
2005-04-12
影响因子：
11.1
作者：
Mothet, JP;Pollegioni, L;Baux, G
通讯作者：
Baux, G
使用患者 iPSC 进行唐氏综合症建模揭示了 GABA 能神经元的细胞和迁移缺陷。
影响因子：
5.9
作者：
Huo HQ;Qu ZY;Yuan F;Ma L;Yao L;Xu M;Hu Y;Ji J;Bhattacharyya A;Zhang SC;Liu Y
通讯作者：
Liu Y