Early-onset of social communication and locomotion activity in F2 pups of a valproic acid-induced mouse model of autism
Early-onset of social communication and locomotion activity in F2 pups of a valproic acid-induced mouse model of autism
复制标题
丙戊酸诱导的自闭症小鼠模型 F2 幼仔的早期社会交流和运动活动
DOI：
10.1016/j.neulet.2022.136827
复制
发表时间：
2022
影响因子：
2.5
通讯作者：
Tsuji T.
中科院分区：
文献类型：
--
作者：
Tsuji C;Furuhara K;Mizutani R;Minami K;Fu P;Zhong J;Higashida H;Yokoyama S;Tsuji T.
自闭症谱系障碍（ASD）是一种异质性广泛性发育障碍，通常发生在3岁之前。精神疾病的动物模型对于阐明潜在的临床前神经机制至关重要。产前暴露于丙戊酸（VPA, F1）的小鼠被广泛用于ASD模型。表观遗传学最近被认为是ASD病因学的一个贡献者，假设表观遗传标记可以跨代遗传。先前的研究表明，在F1 VPA小鼠中检测到的自闭症样行为表型转基因出现在F2和F3代。然而，关于自闭症样行为表型在出生后早期的后代的研究很少。本研究对F2代出生后第5天的行为缺陷进行了检查，以评估ASD症状的发生。通过分析产妇分离引起的超声发声（USVs）来检查沟通障碍。虽然usv的持续时间和频率没有显著改变，但F2 VPA幼崽的排放率显著降低。此外，有配偶或没有配偶的2只VPA幼崽的机车活动发生了变化。目前的研究数据表明，社交缺陷和运动障碍是由下一代遗传的，并且在出生后第5天就很明显了。
Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder that usually occurs before 3 years old. Animal models of psychiatric disorders are essential for elucidating the underlying preclinical neural mechanisms. Mice that are prenatally exposed to valproic acid (VPA, F1) are widely used as an ASD model. Epigenetics has recently been suggested as a contributor to ASD etiology with the hypothesis that epigenetic marks can be transgenerationally inherited. Previous studies have indicated that autism-like behavioral phenotypes detected in F1 VPA mice transgenetically appear in F2 and F3 generations. However, studies on the autism-like behavioral phenotypes during the early postnatal days in subsequent generations are scarce. Here, the behavioral deficit on postnatal day 5 of the F2 generation was examined to assess the onset of ASD symptoms. Communication disorders were examined by analyzing maternal separation-induced ultrasonic vocalizations (USVs). Although the duration and frequency of USVs were not significantly altered, the emission rate was significantly lower in F2 VPA pups. Furthermore, the locomotive activity with or without littermates was altered in F2 VPA pups. The data of the current study suggest that social deficit and impaired locomotion are inherited by the subsequent generation and were apparent on early postnatal day 5.
影响因子：
4.6
作者：
Choi CS;Gonzales EL;Kim KC;Yang SM;Kim JW;Mabunga DF;Cheong JH;Han SH;Bahn GH;Shin CY
通讯作者：
Shin CY
影响因子：
4.8
作者：
Werling DM;Geschwind DH
通讯作者：
Geschwind DH
影响因子：
3.6
作者：
Harris, Susan R.
通讯作者：
Harris, Susan R.