关键词: Autism spectrum disorder Light/dark transition Stereology Thalamus Three-chamber social interaction Valproic acid

Mesh : Animals Valproic Acid / pharmacology Thalamus / drug effects pathology Female Disease Models, Animal Pregnancy Cell Count Rats Behavior, Animal / drug effects Autistic Disorder / chemically induced pathology Neurons / drug effects pathology Rats, Sprague-Dawley Social Behavior Male Autism Spectrum Disorder / chemically induced pathology

来  源:   DOI:10.1016/j.brainres.2024.149047

Abstract:
The contribution of the thalamus to the development and behavioural changes in autism spectrum disorders (ASD), a neurodevelopmental syndrome, remains unclear. The aim of this study was to determine the changes in thalamic volume and cell number in the valproic acid (VPA)-induced ASD model using stereological methods and to clarify the relationship between thalamus and ASD-like behaviour. Ten pregnant rats were administered a single dose (600 mg/kg) of VPA intraperitoneally on G12.5 (VPA group), while five pregnant rats were injected with 5 ml saline (control group). Behavioural tests were performed to determine appropriate subjects and ASD-like behaviours. At P55, the brains of the subjects were removed. The sagittal sections were stained with cresyl violet and toluidine blue. The thalamic and hemispheric volumes with their ratios, the total number of thalamic cells, neurons and non-neuronal cells were calculated using stereological methods. Data were compared using a t-test and a Pearson correlation analysis was performed to examine the relationship between behaviour and stereological outcomes. VPA-treated rats had lower sociability and sociability indexes. There was no difference in social novelty preference and anxiety. The VPA group had larger hemispheric volume, lower thalamic volume, and fewer neurons. The highest percentage decrease was in non-neuronal cells. There was a moderate positive correlation between the number of non-neuronal cells and sociability, thalamic volume and the number of neurons as well as the time spent in the light box. The correlation between behaviour and stereological data suggests that the thalamus is associated with ASD-like behaviour.
摘要:
丘脑对自闭症谱系障碍(ASD)的发育和行为变化的贡献,神经发育综合症,尚不清楚。本研究的目的是使用体视学方法确定丙戊酸(VPA)诱导的ASD模型中丘脑体积和细胞数量的变化,并阐明丘脑与ASD样行为之间的关系。10只孕鼠腹腔注射G12.5单剂量(600mg/kg)VPA(VPA组),五只孕鼠注射5ml生理盐水(对照组)。进行行为测试以确定适当的受试者和ASD样行为。在P55时,移除了受试者的大脑。矢状切片用甲酚紫和甲苯胺蓝染色。丘脑和半球的体积及其比例,丘脑细胞的总数,使用体视学方法计算神经元和非神经元细胞.使用t检验比较数据,并进行Pearson相关分析以检查行为与体视学结果之间的关系。VPA治疗的大鼠社交能力和社交能力指数较低。社会新颖性偏好和焦虑没有差异。VPA组半球体积较大,下丘脑体积,更少的神经元。下降百分比最高的是在非神经元细胞中。非神经元细胞数量与社交能力呈中度正相关,丘脑的体积和神经元的数量以及在光箱中花费的时间。行为和体视学数据之间的相关性表明丘脑与ASD样行为有关。
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