The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.
The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.
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DOI：
10.1038/srep36250
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发表时间：
2016-11-07
影响因子：
4.6
通讯作者：
Shin CY
中科院分区：
文献类型：
--
作者：
Choi CS;Gonzales EL;Kim KC;Yang SM;Kim JW;Mabunga DF;Cheong JH;Han SH;Bahn GH;Shin CY
自闭症谱系障碍（ASD）是一种异质性的广泛性发育障碍，其中各种遗传和环境因素被认为是其发展的基础。最近，表观遗传学已被建议作为一个新的概念，ASD病因学的主张，表观遗传标记可以transgeneratively继承。基于这种表观遗传学的假设，我们研究了ASD样行为的跨代遗传及其相关的突触变化在ASD的VPA动物模型。第一代（F1）VPA暴露的后代表现出自闭症样受损的社交能力和增加大理石掩埋。他们还表现出癫痫易感性增加，多动和焦虑减少。我们将暴露于VPA的F1雄性后代与未经处理的雌性交配以产生第二代（F2），然后将F2类似地交配以产生第三代（F3）。值得注意的是，在F1中发现的自闭症样行为表型持续到F2和F3。此外，F1和F3的额叶皮质表现出兴奋性/抑制性突触标记物的一些不平衡表达，表明跨代表观遗传。这些结果开启了这样一种想法，即由环境损伤诱导的小鼠E/I失衡和ASD样行为变化可以表观遗传地传递到至少第三代。这项研究可以帮助解释ASD患病率前所未有的增加。
Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.
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影响因子：
4.5
作者：
Albert M;Schmitz SU;Kooistra SM;Malatesta M;Morales Torres C;Rekling JC;Johansen JV;Abarrategui I;Helin K
通讯作者：
Helin K
影响因子：
6.9
作者：
BAILEY, A;LECOUTEUR, A;RUTTER, M
通讯作者：
RUTTER, M
DOI：
10.1523/jneurosci.5057-08.2009
发表时间：
2009-02-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Arai JA;Li S;Hartley DM;Feig LA
通讯作者：
Feig LA
DOI：
10.1002/ajmg.1320190308
发表时间：
1984-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
DILIBERTI, JH;FARNDON, PA;CURRY, CJR
通讯作者：
CURRY, CJR
影响因子：
3.5
作者：
Kim, Ki Chan;Kim, Pitna;Ko, Kwang Ho
通讯作者：
Ko, Kwang Ho