HIPPOCAMPAL NEURONAL SUBTYPES DEVELOP ABNORMAL DENDRITIC ARBORS IN THE PRESENCE OF FRAGILE X ASTROCYTES

HIPPOCAMPAL NEURONAL SUBTYPES DEVELOP ABNORMAL DENDRITIC ARBORS IN THE PRESENCE OF FRAGILE X ASTROCYTES
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DOI:
10.1016/j.neuroscience.2016.03.011
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发表时间:
2016-06-02
期刊:
影响因子:
3.3
通讯作者:
Doering, L. C.
Doering, L. C.
中科院分区:
医学3区
文献类型:
--
作者:
Jacobs, S.;Cheng, C.;Doering, L. C.

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星形胶质细胞现在被认为是神经发育障碍如脆性X综合征的神经生物学中的关键参与者。然而,脆性X星形胶质细胞介导的海马神经元亚型树突发育控制的性质尚不清楚。我们使用了共培养程序,其中野生型原代海马神经元与来自野生型或脆性X小鼠的星形胶质细胞一起培养7天、14天或21天。用树突状标记物MAP 2对神经元进行免疫细胞化学处理,按形态学标准分类为五种神经元亚型之一,并进行Sholl分析。Sholl分析的线性和半对数方法都应用于神经元,以提供对树突分支的深入分析。我们发现脆性X星形胶质细胞影响所有野生型海马神经元亚型的树突状分支的发育。此外,我们发现,海马神经元与棘状星状神经元形态表现出最普遍的发育迟缓,与显着的树突乔木改变持续在培养21天。结果进一步表明星形胶质细胞在控制神经元形态学中发挥关键作用,包括脆性X染色体中树突发育的改变。(C)2016年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Astrocytes are now recognized as key players in the neurobiology of neurodevelopmental disorders such as Fragile X syndrome. However, the nature of Fragile X astrocyte-mediated control of dendrite development in sub-types of hippocampal neurons is not yet known. We used a co-culture procedure in which wildtype primary hippocampal neurons were cultured with astrocytes from either a wildtype or Fragile X mouse, for either 7, 14 or 21 days. The neurons were processed for immunocytochemistry with the dendritic marker MAP2, classified by morphological criteria into one of five neuronal subtypes, and subjected to Sholl analyses. Both linear and semi-log methods of Sholl analyses were applied to the neurons in order to provide an in depth analysis of the dendritic arborizations. We found that Fragile X astrocytes affect the development of dendritic arborization of all subtypes of wildtype hippocampal neurons. Furthermore, we show that hippocampal neurons with spiny stellate neuron morphology exhibit the most pervasive developmental delays, with significant dendritic arbor alterations persisting at 21 days in culture. The results further dictate the critical role astrocytes play in governing neuronal morphology including altered dendrite development in Fragile X. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.