Lithium ameliorates autistic-like behaviors induced by neonatal isolation in rats.
Lithium ameliorates autistic-like behaviors induced by neonatal isolation in rats.
复制标题
锂可改善大鼠新生儿隔离引起的自闭症样行为
DOI：
10.3389/fnbeh.2014.00234
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发表时间：
2014
影响因子：
3
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
Wu X;Bai Y;Tan T;Li H;Xia S;Chang X;Zhou Z;Zhou W;Li T;Wang YT;Dong Z
新生儿隔离是一种被广泛接受的研究早期生活事件所产生的长期行为变化的模型。然而，新生儿隔离是否能诱导类似自闭症的行为，如果是这样，药物治疗是否可以克服它仍然是未知的。在这里，我们报告了新生大鼠从出生后1-9天每天与母亲和巢单独隔离1小时，表现出明显的类似自闭症的症状，包括社会缺陷，过度重复的自我修饰行为，并且与正常饲养的对照相比，在年轻成年人（出生后42-56天）中测试的焦虑和抑郁样行为增加。此外，这些行为的变化伴随着受损的成年海马神经发生和减少的兴奋性/抑制性突触传递的比例，反映了自发抑制性突触后电流（sIPSC）和正常的自发兴奋性突触后电流（sEPSC）在海马CA 1锥体神经元的增加。更重要的是，长期服用锂（一种临床使用的情绪稳定剂）完全克服了新生儿隔离诱导的自闭症样行为，并恢复了成年海马神经发生以及兴奋和抑制活动之间的平衡。这些发现表明，新生儿隔离可能会产生类似自闭症的行为，锂可能是一种潜在的治疗药物，对自闭症谱系障碍（ASD）在发展过程中。
Neonatal isolation is a widely accepted model to study the long-term behavioral changes produced by the early life events. However, it remains unknown whether neonatal isolation can induce autistic-like behaviors, and if so, whether pharmacological treatment can overcome it. Here, we reported that newborn rats subjected to individual isolations from their mother and nest for 1 h per day from postnatal days 1–9 displayed apparent autistic-like symptoms including social deficits, excessive repetitive self-grooming behavior, and increased anxiety- and depressive-like behaviors tested in young adult (postnatal days 42–56) compared to normal reared controls. Furthermore, these behavioral changes were accompanied by impaired adult hippocampal neurogenesis and reduced the ratio of excitatory/inhibitory synaptic transmissions, as reflected by an increase in spontaneous inhibitory postsynaptic current (sIPSC) and normal spontaneous excitatory postsynaptic current (sEPSC) in the hippocampal CA1 pyramidal neuron. More importantly, chronic administration of lithium, a clinically used mood stabilizer, completely overcame neonatal isolation-induced autistic-like behaviors, and restored adult hippocampal neurogenesis as well as the balance between excitatory and inhibitory activities to physiological levels. These findings indicate that neonatal isolation may produce autistic-like behaviors, and lithium may be a potential therapeutic agent against autism spectrum disorders (ASD) during development.
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