Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice.
Gene-environment interactions affect long-term depression (LTD) through changes in dopamine receptor affinity in Snap25 deficient mice.
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DOI：
10.1016/j.brainres.2013.08.012
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发表时间：
2013-09-26
期刊：
影响因子：
2.9
通讯作者：
Wilson MC
中科院分区：
文献类型：
--
作者：
Baca M;Allan AM;Partridge LD;Wilson MC
基因和环境条件在认知能力的发展中相互作用，并且每一种都在神经精神障碍如注意力缺陷/多动障碍（ADHD）和精神分裂症中发挥重要作用。多项研究表明，SNARE蛋白SNAP-25基因是ADHD和精神分裂症的候选易感基因，而母亲吸烟是ADHD的候选环境风险因素。我们利用SNAP-25无效等位基因杂合子和SNAP-25表达缺陷的小鼠，结合产前暴露于尼古丁来模拟遗传效应，以探索突触可塑性和行为中的遗传和环境相互作用。我们发现，SNAP-25缺陷小鼠暴露于产前尼古丁表现出多动症和赤字的社会互动。使用高频刺激电生理范式长期抑郁症（LTD）诱导，我们研究了多巴胺D2受体（D2 Rs）和大麻素CB 1受体（CB 1 Rs）的作用，这两个关键的LTD诱导纹状体。我们发现，产前暴露于尼古丁的Snap 25杂合子无效小鼠产生的D2 R依赖性诱导LTD的赤字，虽然CB 1 R调节的可塑性没有受损。我们还表明，产前尼古丁暴露改变了D2 Rs的亲和力和/或受体偶联，但不是杂合子无效Snap 25突变体中这些受体的数量。这些结果完善了在缺损小鼠突变体（一种拟议的ADHD小鼠模型）中的观察结果，并说明了基因×环境的影响如何相互作用，干扰调节行为的神经功能。
Genes and environmental conditions interact in the development of cognitive capacities and each plays an important role in neuropsychiatric disorders such as attention deficit/hyperactivity disorder (ADHD) and schizophrenia. Multiple studies have indicated that the gene for the SNARE protein SNAP-25 is a candidate susceptibility gene for ADHD, as well as schizophrenia, while maternal smoking is a candidate environmental risk factor for ADHD. We utilized mice heterozygous for a Snap25 null allele and deficient in SNAP-25 expression to model genetic effects in combination with prenatal exposure to nicotine to explore genetic and environmental interactions in synaptic plasticity and behavior. We show that SNAP-25 deficient mice exposed to prenatal nicotine exhibit hyperactivity and deficits in social interaction. Using a high frequency stimulus electrophysiological paradigm for long-term depression (LTD) induction, we examined the roles of dopaminergic D2 receptors (D2Rs) and cannabinoid CB1 receptors (CB1Rs), both critical for LTD induction in the striatum. We found that prenatal exposure to nicotine in Snap25 heterozygote null mice produced a deficit in the D2R-dependent induction of LTD, although CB1R regulation of plasticity was not impaired. We also show that prenatal nicotine exposure altered the affinity and/or receptor coupling of D2Rs, but not the number of these receptors in heterozygote null Snap25 mutants. These results refine the observations made in the coloboma mouse mutant, a proposed mouse model of ADHD, and illustrate how gene × environmental influences can interact to perturb neural functions that regulate behavior.
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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美国儿童的环境有毒物质和注意力缺陷多动障碍的暴露。
影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.psc.2009.12.004
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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