Sex differences in autism-like behavior and dopaminergic neurons in substantia nigra of juvenile mice prenatally exposed to valproate

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
David Zarate-Lopez, Andrea P. Garzón-Partida, Oscar Gonzalez-Perez, Alma Y. Gálvez-Contreras
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Abstract

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication and repetitive and restricted behaviors. Sex dimorphism in the brain, including midbrain dopaminergic circuits, can explain differences in social behavior impairment and stereotypic behaviors between male and female individuals with ASD. These abnormal patterns may be due to alterations in dopamine synthesis in the ventral tegmental area (VTA) and substantia nigra (SN). We used an autism-like mouse model by prenatal valproic acid (VPA) exposure. CD1 pregnant female mice were injected with 500 mg/kg VPA or 0.9% NaCl as a vehicle on gestational day 12.5. In the offspring, on postnatal day 31, we examined the social and repetitive behaviors and the number of tyrosine hydroxylase (TH)-positive cells in VTA and SN by sex. Male VPA mice showed impaired social behavior and increased repetitive behaviors when compared to male vehicles. In females, we did not find statistically significant differences in social or repetitive behaviors between the groups. Male VPA mice had fewer TH+ cells in the SN than control-vehicle mice. Interestingly, no cellular changes were observed between females. This study supports the notion that sex dimorphism of certain brain regions is involved in the etiopathogenesis and clinical presentation of ASD.

产前接触丙戊酸钠的幼鼠自闭症样行为和黑质多巴胺能神经元的性别差异
自闭症谱系障碍(ASD)的特点是社交互动和交流障碍以及重复和受限行为。大脑(包括中脑多巴胺能回路)的性别二形性可以解释自闭症谱系障碍男女患者在社交行为障碍和刻板行为方面的差异。这些异常模式可能是由于腹侧被盖区(VTA)和黑质(SN)的多巴胺合成发生了改变。我们利用产前丙戊酸(VPA)暴露建立了一个类似自闭症的小鼠模型。在妊娠第 12.5 天,给 CD1 怀孕雌性小鼠注射 500 毫克/千克 VPA 或 0.9% 氯化钠作为载体。在后代出生后第31天,我们按性别检测了其社交和重复行为以及VTA和SN中酪氨酸羟化酶(TH)阳性细胞的数量。与雄性车辆相比,雄性VPA小鼠的社交行为受损,重复行为增加。在雌性小鼠中,我们没有发现各组之间在社交或重复行为方面存在显著的统计学差异。与对照组小鼠相比,雄性 VPA 小鼠鼻窦中的 TH+ 细胞更少。有趣的是,雌性之间没有观察到细胞变化。这项研究支持这样一种观点,即某些脑区的性别二形性与 ASD 的发病机制和临床表现有关。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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