Laszlo Kristof, Bacova Zuzana, Zelena Dora, Bakos Jan
Medical School, Institute of Physiology, University of Pecs, Pecs, Hungary.
Neuropeptides, Cognition, Animal Models of Neuropsychiatric Disorders Research Group, Medical School, Institute of Physiology, University of Pecs, Pecs, Hungary.
Dev Neurobiol. 2025 Jul;85(3):e22977. doi: 10.1002/dneu.22977.
Although the early signs of autism spectrum disorder (ASD) are widely studied, the significant ambiguity and heterogeneity in symptoms require the comparison of available models, approaches, and the search for common denominators and key indicators. Early ASD symptoms in animal models include impaired somatic development (e.g., delayed eye opening), alterations in primitive motor reflexes, disrupted sensory function as well as communication deficits, such as reduced ultrasonic vocalization. This review aims to summarize early ASD-related symptoms based on studies involving transgenic or neurotoxic rodent models (postnatal days 1-21) and to compare these with human resemblance. The key brain areas (subventricular zone, cortex, hippocampus, cerebellum, etc.) as well as relevant neurotransmitter systems (GABA-glutamate imbalance, developmental GABA shift, serotonin, dopamine, oxytocin [OT], etc.) were identified as potential targets for intervention. OT, although a promising candidate, exemplifies the translational challenges inherent in ASD research. Therefore, it is recommended to monitor a wide range of behavioral signs simultaneously and employ diverse models (e.g., genetic, developmental, environmental, or combination) in preclinical studies to more accurately reflect the complexity of the disorder.
尽管自闭症谱系障碍(ASD)的早期症状得到了广泛研究,但症状中存在的显著模糊性和异质性需要对现有模型、方法进行比较,并寻找共同特征和关键指标。动物模型中的早期ASD症状包括躯体发育受损(如睁眼延迟)、原始运动反射改变、感觉功能紊乱以及交流缺陷,如超声发声减少。本综述旨在基于涉及转基因或神经毒性啮齿动物模型(出生后第1 - 21天)的研究,总结与早期ASD相关的症状,并将其与人类相似症状进行比较。关键脑区(脑室下区、皮层、海马体、小脑等)以及相关神经递质系统(γ-氨基丁酸 - 谷氨酸失衡、发育性γ-氨基丁酸转变、血清素、多巴胺、催产素[OT]等)被确定为潜在的干预靶点。OT虽然是一个有前景的候选靶点,但体现了ASD研究中固有的转化挑战。因此,建议在临床前研究中同时监测广泛的行为体征,并采用多种模型(如基因、发育、环境或联合模型),以更准确地反映该疾病的复杂性。