Department of Morphological Sciences and Teratology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel.
Hadassah Academic College, Jerusalem 9101001, Israel.
Int J Mol Sci. 2024 Sep 28;25(19):10469. doi: 10.3390/ijms251910469.
Appropriate animal models of human diseases are a cornerstone in the advancement of science and medicine. To create animal models of neuropsychiatric and neurobehavioral diseases such as autism spectrum disorder (ASD) necessitates the development of sufficient neurobehavioral measuring tools to translate human behavior to expected measurable behavioral features in animals. If possible, the severity of the symptoms should also be assessed. Indeed, at least in rodents, adequate neurobehavioral and neurological tests have been developed. Since ASD is characterized by a number of specific behavioral trends with significant severity, animal models of autistic-like behavior have to demonstrate the specific characteristic features, namely impaired social interactions, communication deficits, and restricted, repetitive behavioral patterns, with association to several additional impairments such as somatosensory, motor, and memory impairments. Thus, an appropriate model must show behavioral impairment of a minimal number of neurobehavioral characteristics using an adequate number of behavioral tests. The proper animal models enable the study of ASD-like-behavior from the etiologic, pathogenetic, and therapeutic aspects. From the etiologic aspects, models have been developed by the use of immunogenic substances like polyinosinic-polycytidylic acid (PolyIC), lipopolysaccharide (LPS), and propionic acid, or other well-documented immunogens or pathogens, like Another approach is the use of chemicals like valproic acid, polychlorinated biphenyls (PCBs), organophosphate pesticides like chlorpyrifos (CPF), and others. These substances were administered either prenatally, generally after the period of major organogenesis, or, especially in rodents, during early postnatal life. In addition, using modern genetic manipulation methods, genetic models have been created of almost all human genetic diseases that are manifested by autistic-like behavior (i.e., fragile X, Rett syndrome, SHANK gene mutation, neuroligin genes, and others). Ideally, we should not only evaluate the different behavioral modes affected by the ASD-like behavior, but also assess the severity of the behavioral deviations by an appropriate scoring system, as applied to humans. We therefore propose a scoring system for improved assessment of ASD-like behavior in animal models.
适当的人类疾病动物模型是科学和医学进步的基石。为了创建神经精神和神经行为疾病（如自闭症谱系障碍 (ASD)）的动物模型，需要开发足够的神经行为测量工具，以便将人类行为转化为动物预期的可测量行为特征。如果可能的话，还需要评估症状的严重程度。事实上，至少在啮齿动物中，已经开发出了足够的神经行为和神经学测试。由于 ASD 的特征是具有显著严重程度的一系列特定行为趋势，因此，类似自闭症行为的动物模型必须表现出特定的特征，即社交互动受损、沟通障碍和受限、重复的行为模式，以及与其他一些障碍相关，如感觉、运动和记忆障碍。因此，适当的模型必须使用足够数量的行为测试，表现出最少数量的神经行为特征的行为损伤。适当的动物模型可以从病因学、发病机制和治疗学方面研究类似 ASD 的行为。从病因学方面，已经通过使用免疫原性物质（如聚肌胞苷酸、脂多糖和丙酸）或其他有充分记录的免疫原或病原体（如多聚 I:C、脂多糖和丙酸）开发了模型。另一种方法是使用化学物质，如丙戊酸、多氯联苯 (PCBs)、有机磷杀虫剂如毒死蜱 (CPF) 等。这些物质要么在产前，通常在主要器官发生期之后，要么在早期产后生活中，尤其是在啮齿动物中给予。此外，使用现代遗传操作方法，已经创建了几乎所有表现出类似自闭症行为的人类遗传疾病的遗传模型（即脆性 X 综合征、雷特综合征、SHANK 基因突变、神经连接蛋白基因等）。理想情况下，我们不仅要评估受类似 ASD 行为影响的不同行为模式，还要通过适当的评分系统评估行为偏差的严重程度，就像在人类中一样。因此，我们提出了一种评分系统，用于改进动物模型中类似 ASD 行为的评估。
