母体用阿立哌唑治疗可防止幼年雄性小鼠丙戊酸诱导的自闭症样表型的发展。

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES
Emerson de Oliveira Ferreira, Jéssica Maria Pessoa Gomes, Kelly Rose Tavares Neves, Francisco Arnaldo Viana Lima, Glauce Socorro de Barros Viana, Geanne Matos de Andrade
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引用次数: 1

摘要

自闭症谱系障碍(ASD)描述了一组异质性的神经发育状况,其特征是社会沟通和重复行为的缺陷。阿立哌唑(APZ)是一种非典型抗精神病药,可以保护小鼠免受丙戊酸(VPA)诱导的自闭症样行为。在本研究中,我们研究了母体给予APZ (10 mg/kg)对幼年期暴露于VPA的小鼠神经发育行为、社会互动、交流和工作记忆的影响,以及内侧前额叶皮层(mPFC)突触素(SYP)、突触体相关蛋白、25 kDa (SNAP-25)和微管相关蛋白2 (MAP-2)表达和海马细胞活力的影响。此外,评估APZ可能干扰VPA对戊四唑(PTZ)诱发癫痫发作的抗惊厥特性。母亲用APZ治疗可以显著预防VPA暴露小鼠的体重减轻、自我矫正、睁眼、社会互动、社会沟通和工作记忆缺陷。此外,APZ可阻止mPFC中SYP、SNAP-25和MAP-2表达的降低和海马细胞死亡。此外,APZ (10 mg/kg)不会干扰VPA (15 mg/kg)对ptz诱导癫痫发作动物的抗惊厥作用。这些发现表明,母体给暴露于VPA的怀孕小鼠注射APZ可以保护动物免受asd样行为表型的影响,这种影响可能至少部分与PFC和海马的突触可塑性和神经元保护有关。在ASD VPA动物模型中,APZ可能作为一种有效的药物治疗靶点,其临床意义有待进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Maternal treatment with aripiprazole prevents the development of a valproic acid-induced autism-like phenotype in juvenile male mice.

Autism spectrum disorder (ASD) describes a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and repetitive behaviors. Aripiprazole (APZ) is an atypical antipsychotic that can safeguard mice against autism-like behavior induced by valproic acid (VPA). In the present study, we examined the effects of maternal treatment with APZ (10 mg/kg) in juvenile mice prenatally exposed to VPA on neurodevelopmental behaviors, social interactions, communication, and working memory, as well as synaptophysin (SYP), synaptosomal-associated protein, 25 kDa (SNAP-25) and microtubule-associated protein 2 (MAP-2) expression in the medial prefrontal cortex (mPFC) and cell viability in the hippocampus. In addition, to evaluate possible APZ interference with the anticonvulsant properties of VPA on pentylenetetrazole (PTZ)-induced seizures were evaluated. Maternal treatment with APZ significantly prevented body weight loss, self-righting, eye-opening, social interactions, social communication, and working memory deficits in mice prenatally exposed to VPA. Additionally, the decrease in the SYP, SNAP-25, and MAP-2 expressions in the mPFC and cell death in the hippocampus was prevented by APZ. Furthermore, APZ (10 mg/kg) did not interfere with the anticonvulsant effect of VPA (15 mg/kg) in animals with PTZ-induced seizures. These findings indicate that maternal treatment with APZ in pregnant mice exposed to VPA protects animals against the ASD-like behavioral phenotype, and this effect may be related, at least in part, to synaptic plasticity and neuronal protection in the PFC and hippocampus. APZ may serve as an effective pharmacological therapeutic target against autistic behaviors in the VPA animal model of ASD, which should be further investigated to verify its clinical relevance.

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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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