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自闭症样行为和丘脑细胞数量变化——丙戊酸诱导自闭症大鼠模型:一项行为学和体视学研究。

Autistic-like behaviour and changes in thalamic cell numbers a rat model of valproic acid-induced autism; A behavioural and stereological study.

机构信息

Orthopedic Prosthesis Orthotics, Atatürk Health Services Vocational School, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey.

Department of Anatomy, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.

出版信息

Brain Res. 2024 Oct 1;1840:149047. doi: 10.1016/j.brainres.2024.149047. Epub 2024 May 31.

DOI:10.1016/j.brainres.2024.149047
PMID:38823508
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

丘脑在自闭症谱系障碍(ASD)等神经发育综合征的发展和行为变化中的作用尚不清楚。本研究旨在通过体视学法确定丙戊酸(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 只怀孕大鼠在 G12.5 时腹腔内给予单次剂量(600mg/kg)VPA(VPA 组),而 5 只怀孕大鼠注射 5ml 生理盐水(对照组)。进行行为测试以确定合适的对象和 ASD 样行为。在 P55,取出对象的大脑。用甲苯胺蓝和甲苯胺蓝对矢状切片进行染色。使用体视学法计算丘脑和半球体积及其比率、丘脑细胞总数、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 处理的大鼠社交能力和社交指数较低。社会新颖性偏好和焦虑没有差异。VPA 组半球体积较大,丘脑体积较小,神经元较少。非神经元细胞的百分比下降最大。非神经元细胞数量与社交能力、丘脑体积和神经元数量以及在亮箱中花费的时间之间存在中度正相关。行为与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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Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model.在丙戊酸诱导的自闭症模型中,尽管丘脑微透析液中的细胞数量减少,但血清素水平升高,谷氨酸和γ-氨基丁酸水平未变。
Neurochem Res. 2024 Dec 5;50(1):45. doi: 10.1007/s11064-024-04299-2.