Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism
Prevention of behavioral deficits in rats exposed to folate receptor antibodies: implication in autism
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DOI：
10.1038/mp.2016.153
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发表时间：
2017-09-01
影响因子：
11
通讯作者：
Quadros, E. V.
中科院分区：
文献类型：
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作者：
Desai, A.;Sequeira, J. M.;Quadros, E. V.
叶酸受体 α (FR α) 自身抗体与胎儿畸形和脑叶酸缺乏相关的发育障碍有关。超过 70% 的自闭症谱系障碍 (ASD) 儿童的自身抗体呈阳性，高剂量亚叶酸对治疗这些儿童有益。在这里，我们发现，在妊娠期间给予大鼠 FRa 的抗体 (Abs) 会在大鼠模型中产生沟通、学习和认知缺陷，而亚叶酸和地塞米松可以预防这种缺陷。 FR α Ab 可以引发炎症，并阻止叶酸向胎儿和发育中的大脑输送，从而产生功能缺陷。对于人类来说，在胎儿发育和婴儿期接触 FR α 自身抗体可能会导致大脑功能障碍，例如自闭症谱系障碍 (ASD) 和其他发育障碍中所见的情况。识别自身抗体呈阳性的女性并用高剂量亚叶酸治疗以及其他降低自身抗体滴度的干预措施是可以考虑降低生育发育缺陷儿童的风险的有效策略。
Folate receptor alpha (FR alpha) autoantibodies have been associated with fetal abnormalities and cerebral folate deficiency-related developmental disorders. Over 70% of the children with autism spectrum disorders (ASD) are positive for these autoantibodies and high-dose folinic acid is beneficial in treating these children. Here we show that antibodies (Abs) to the rat FRa administered during gestation produce communication, learning and cognitive deficits in a rat model that can be prevented by folinic acid and dexamethasone. FR alpha Ab can trigger inflammation as well as block folate transport to the fetus and to the developing brain to produce the functional deficits. In humans, exposure to FR alpha autoantibodies during fetal development and infancy could contribute to brain dysfunction such as that seen in ASD and other developmental disorders. Identifying women positive for the autoantibody and treating them with high-dose folinic acid along with other interventions to lower the autoantibody titer are effective strategies that may be considered to reduce the risk of having a child with developmental deficits.