Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model
Maternal Stress Combined with Terbutaline Leads to Comorbid Autistic-Like Behavior and Epilepsy in a Rat Model
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DOI：
10.1523/jneurosci.2803-15.2015
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发表时间：
2015-12-02
影响因子：
5.3
通讯作者：
Barth, Daniel S.
中科院分区：
文献类型：
--
作者：
Bercum, Florencia M.;Rodgers, Krista M.;Barth, Daniel S.
人类自闭症与癫痫共病，然而，人们对导致这种联合神经系统综合征的原因或风险因素知之甚少。虽然遗传易感性可以发挥重要作用，我们的目标是调查是否母亲的环境因素单独可能是sufficient.We检查的独立和联合的影响，母亲的压力和特布他林（用于逮捕早产），孤独症的危险因素在人类，对自闭症样行为和癫痫的措施在Sprague-Dawley大鼠。妊娠母鼠在整个妊娠期间暴露于轻度应激（间隔1周的足部电击）。在出生后第2- 5天注射特布他林。母体应激或特布他林均可导致子代出现类似自闭症的行为（刻板/重复行为和社交或沟通障碍），但均未导致癫痫。然而，它们的组合导致了严重的行为症状，以及45%的大鼠自发性反复惊厥发作和100%的大鼠癫痫样棘波。海马神经胶质增生症（GFAP反应性）与异常行为和自发性癫痫发作相关，我们得出结论，产前损伤单独可导致自闭症和癫痫共病，但它需要致畸剂的组合来实现这一点;单独测试单一致畸剂，而不是检查组合效应可能无法揭示人类的关键风险因素。此外，星形胶质细胞增生可能是共同的两种致畸剂。这种新的自闭症和癫痫相结合的动物模型允许实验研究的细胞机制和潜在的干预策略，这种衰弱的共病综合征。
Human autism is comorbid with epilepsy, yet, little is known about the causes or risk factors leading to this combined neurological syndrome. Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient.We examined the independent and combined effects of maternal stress and terbutaline (used to arrest preterm labor), autism risk factors in humans, on measures of both autistic-like behavior and epilepsy in Sprague-Dawley rats. Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with terbutaline on postnatal days 2-5.Either maternal stress or terbutaline resulted in autistic-like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in epilepsy. However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent convulsive seizures in 45% and epileptiform spikes in 100%, of the rats. Hippocampal gliosis (GFAP reactivity) was correlated with both abnormal behavior and spontaneous seizures.We conclude that prenatal insults alone can cause comorbid autism and epilepsy but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in humans. Moreover, astrogliosis may be common to both teratogens. This new animal model of combined autism and epilepsy permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome.