Maternal autoimmune antibodies alter the dendritic arbor and spine numbers in the infragranular layers of the cortex.
Maternal autoimmune antibodies alter the dendritic arbor and spine numbers in the infragranular layers of the cortex.
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DOI：
10.1371/journal.pone.0183443
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Martínez-Cerdeño V
中科院分区：
文献类型：
--
作者：
Ariza J;Hurtado J;Rogers H;Ikeda R;Dill M;Steward C;Creary D;Van de Water J;Martínez-Cerdeño V
母体 IgG 抗体对胎儿大脑中的蛋白质具有反应性，与儿童自闭症的结果之间的关联已被确定。使用产前脑室内注射自闭症特异性母体 IgG 的小鼠模型，我们证明这些抗体会产生与自闭症儿童相似的行为改变。我们之前证明这些抗体与放射状胶质干细胞（RG）结合，并观察到发育中的皮层中 RG 易位分裂数量的增加。我们还发现成年小鼠的大脑大小发生了变化，神经元体积普遍增加。在这里，我们使用心室内注射抗体的小鼠模型，然后进行高尔基体和 Neurolucida 分析，以证明在神经发生中期，这些母体自闭症特异性抗体在分析的成人皮质区域的颗粒下层中的棘数量持续减少。具体而言，在额叶皮质中，第五层神经元的基底树突的长度和体积均减少，并且成熟和未成熟的棘总数以及棘密度均低于同一区域的对照神经元。此外，在枕叶皮质第VI层神经元中，顶树突中的棘总数和棘密度减少，以及顶树突和基底树突中的成熟棘数量减少。有趣的是，暴露于这些抗体（E14.5）的时间与额叶皮质第五层和枕叶皮质第六层锥体神经元的生成一致，遵循皮质细胞生成的正常头尾模式。我们最近证明，这些抗体识别的主要抗原之一对应于应激诱导的磷蛋白 1 (STIP1)。在这里，我们假设发育中的皮质中新生细胞接触 STIP1 的减少可能是我们在成人皮质中注意到的树突分枝和棘数量减少的原因。
An association between maternal IgG antibodies reactive against proteins in fetal brain and an outcome of autism in the child has been identified. Using a mouse model of prenatal intraventricular administration of autism-specific maternal IgG, we demonstrated that these antibodies produce behavioral alterations similar to those in children with ASD. We previously demonstrated that these antibodies bind to radial glial stem cells (RG) and observed an increase in the number of divisions of translocating RG in the developing cortex. We also showed an alteration in brain size and as well as a generalized increased of neuronal volume in adult mice. Here, we used our intraventricular mouse model of antibody administration, followed by Golgi and Neurolucida analysis to demonstrate that during midstages of neurogenesis these maternal autism-specific antibodies produced a consistent decrease in the number of spines in the infragranular layers in the adult cortical areas analyzed. Specifically, in the frontal cortex basal dendrites of layer V neurons were decreased in length and volume, and both the total number of spines—mature and immature—and the spine density were lower than in the control neurons from the same region. Further, in the occipital cortex layer VI neurons presented with a decrease in the total number of spines and in the spine density in the apical dendrite, as well as decrease in the number of mature spines in the apical and basal dendrites. Interestingly, the time of exposure to these antibodies (E14.5) coincides with the generation of pyramidal neurons in layer V in the frontal cortex and in layer VI in the occipital cortex, following the normal rostro-caudal pattern of cortical cell generation. We recently demonstrated that one of the primary antigens recognized by these antibodies corresponds to stress-induced phosphoprotein 1 (STIP1). Here we hypothesize that the reduction in the access of newborn cells to STIP1 in the developing cortex may be responsible for the reduced dendritic arborization and number of spines we noted in the adult cortex.
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影响因子：
6.2
作者：
Arantes, Camila;Nomiz, Regina;Martins, Vilma R.
通讯作者：
Martins, Vilma R.
影响因子：
2.7
作者：
Camacho J;Jones K;Miller E;Ariza J;Noctor S;de Water JV;Martínez-Cerdeño V
通讯作者：
Martínez-Cerdeño V
自闭症的神经病理学。
影响因子：
3.2
作者：
Blatt GJ
通讯作者：
Blatt GJ
影响因子：
3.7
作者：
Hashimoto T;Hussien R;Cho HS;Kaufer D;Brooks GA
通讯作者：
Brooks GA
影响因子：
5.1
作者：
Charrier, E;Reibel, S;Honnorat, J
通讯作者：
Honnorat, J