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17-β estradiol increases parvalbumin levels in Pvalb heterozygous mice and attenuates behavioral phenotypes with relevance to autism core symptoms.
Molecular Autism ( IF 6.2 ) Pub Date : 2018-03-07 , DOI: 10.1186/s13229-018-0199-3
Federica Filice 1 , Emanuel Lauber 1 , Karl Jakob Vörckel 2 , Markus Wöhr 2, 3 , Beat Schwaller 1
Affiliation  

Background Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by two core symptoms: impaired social interaction and communication, and restricted, repetitive behaviors and interests. The pathophysiology of ASD is not yet fully understood, due to a plethora of genetic and environmental risk factors that might be associated with or causal for ASD. Recent findings suggest that one putative convergent pathway for some forms of ASD might be the downregulation of the calcium-binding protein parvalbumin (PV). PV-deficient mice (PV-/-, PV+/-), as well as Shank1-/-, Shank3-/-, and VPA mice, which show behavioral deficits relevant to all human ASD core symptoms, are all characterized by lower PV expression levels. Methods Based on the hypothesis that PV expression might be increased by 17-β estradiol (E2), PV+/- mice were treated with E2 from postnatal days 5-15 and ASD-related behavior was tested between postnatal days 25 and 31. Results PV expression levels were significantly increased after E2 treatment and, concomitantly, sociability deficits in PV+/- mice in the direct reciprocal social interaction and the 3-chamber social approach assay, as well as repetitive behaviors, were attenuated. E2 treatment of PV+/+ mice did not increase PV levels and had detrimental effects on sociability and repetitive behavior. In PV-/- mice, E2 obviously did not affect PV levels; tested behaviors were not different from the ones in vehicle-treated PV-/- mice. Conclusion Our results suggest that the E2-linked amelioration of ASD-like behaviors is specifically occurring in PV+/- mice, indicating that PV upregulation is required for the E2-mediated rescue of ASD-relevant behavioral impairments.

中文翻译:

17-β雌二醇可增加Pvalb杂合小鼠的小白蛋白水平,并减弱与自闭症核心症状相关的行为表型。

背景自闭症谱系障碍(ASD)是一组神经发育障碍,其特征是两个核心症状:社交互动和沟通受损,以及重复性行为和兴趣受到限制。由于可能与ASD相关或成因的大量遗传和环境风险因素,ASD的病理生理学尚未完全了解。最近的发现表明,某些形式的ASD的一种可能的收敛途径可能是钙结合蛋白小白蛋白(PV)的下调。PV缺陷小鼠(PV-/-,PV +/-)以及Shank1-/-,Shank3-/-和VPA小鼠均表现出与所有人类ASD核心症状相关的行为缺陷,均以较低的PV为特征表达水平。方法基于17-β雌二醇(E2)可能增加PV表达的假设,从出生后第5-15天开始用E2治疗PV +/-小鼠,并在出生后第25至31天之间测试ASD相关行为。结果E2治疗后PV表达水平显着增加,因此,相互直接的社交互动和三室社交方法的测定以及重复性行为被削弱。E2处理PV + / +小鼠不会增加PV水平,并且对社交性和重复行为具有有害影响。在PV-/-小鼠中,E2显然不会影响PV水平;相反,E2不会影响PV水平。测试的行为与载体治疗的PV-/-小鼠的行为没有不同。结论我们的结果表明E2联动改善ASD样行为在PV +/-小鼠中特别发生,
更新日期:2019-11-01
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