Construction of an animal model of autism based on interaction between cerebellar histological, immunohistochemical, and biochemical changes in adult male albino rat.

IF 1.1 4区 医学 Q4 MICROSCOPY Ultrastructural Pathology Pub Date : 2025-01-02 Epub Date: 2024-12-09 DOI:10.1080/01913123.2024.2438382
Eman Saeed Mokhtar Tawfeek, Salwa Aly Abou Elez Gawish, Wafaa Saad Hamed, Samar A Asker
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Abstract

Methods: Twelve pregnant female rats were divided into a control group and a valproic acid (VPA) treated group (injected intraperitoneally on embryonic day 12 with 600 mg/kg body weight of VPA). Neurobehavioral tests were conducted on the offspring of both groups. The cerebellum was studied by light and electron microscopy as well as GFAP and caspase-3 immunohistochemical staining.

Results: The VPA-treated group showed signs of neuronal degeneration, such as congested blood vessels, vacuolations, irregularly shrunken with dark small heterochromatic nuclei and numerous apoptotic blebs in the Purkinje and granule cells with vacuolated cerebellar glomeruli. The myelinated nerve fibers showed rarefaction and loss of their neurofilaments. GFAP and caspase-3 immune expression were significantly altered in the VPA-treated group.

Conclusion: The VPA rat model can serve as an excellent model of autism at the structural level, which may be used as a validated model in preclinical studies to evaluate novel drugs.

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基于成年雄性白化大鼠小脑组织学、免疫组织化学和生化变化相互作用的自闭症动物模型的构建。
方法:将12只怀孕雌性大鼠分为对照组和丙戊酸(VPA)处理组(在胚胎第12天腹腔注射600 mg/kg体重的VPA)。对两组的后代都进行了神经行为测试。采用光镜、电镜、GFAP和caspase-3免疫组化染色对大鼠小脑进行观察。结果:vpa处理组出现神经退行性变,如血管充血、空泡化、不规则萎缩、暗小异色核、浦肯野细胞大量凋亡泡和小脑肾小球空泡化颗粒细胞。髓鞘神经纤维稀疏,神经丝缺失。vpa处理组GFAP和caspase-3免疫表达明显改变。结论:VPA大鼠模型在结构水平上是一种很好的自闭症模型,可作为临床前研究中新药评价的验证模型。
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来源期刊
Ultrastructural Pathology
Ultrastructural Pathology 医学-病理学
CiteScore
2.00
自引率
10.00%
发文量
40
审稿时长
6-12 weeks
期刊介绍: Ultrastructural Pathology is the official journal of the Society for Ultrastructural Pathology. Published bimonthly, we are the only journal to be devoted entirely to diagnostic ultrastructural pathology. Ultrastructural Pathology is the ideal journal to publish high-quality research on the following topics: Advances in the uses of electron microscopic and immunohistochemical techniques Correlations of ultrastructural data with light microscopy, histochemistry, immunohistochemistry, biochemistry, cell and tissue culturing, and electron probe analysis Important new, investigative, clinical, and diagnostic EM methods.
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