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自闭症谱系障碍动物模型中的发育障碍

Developmental Disturbances in Animal Models of Autism Spectrum Disorder.

作者信息

Laszlo Kristof, Bacova Zuzana, Zelena Dora, Bakos Jan

机构信息

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.

出版信息

Dev Neurobiol. 2025 Jul;85(3):e22977. doi: 10.1002/dneu.22977.

DOI:10.1002/dneu.22977
PMID:40495546
Abstract

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.

摘要

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。

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Developmental Disturbances in Animal Models of Autism Spectrum Disorder.自闭症谱系障碍动物模型中的发育障碍
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本文引用的文献

1
Early movement restriction impairs the development of sensorimotor integration, motor skills and memory in rats: Towards a preclinical model of developmental coordination disorder?早期运动限制会损害大鼠的感觉运动整合、运动技能和记忆发展:迈向发育协调障碍的临床前模型?
Eur J Neurosci. 2024 Dec;60(11):6830-6850. doi: 10.1111/ejn.16594. Epub 2024 Nov 10.
2
Animal Models of Autistic-like Behavior in Rodents: A Scoping Review and Call for a Comprehensive Scoring System.啮齿类动物自闭症样行为的动物模型:范围综述及呼吁建立全面的评分系统。
Int J Mol Sci. 2024 Sep 28;25(19):10469. doi: 10.3390/ijms251910469.
3
Prenatal environmental risk factors for autism spectrum disorder and their potential mechanisms.
自闭症谱系障碍的产前环境风险因素及其潜在机制。
BMC Med. 2024 Sep 16;22(1):393. doi: 10.1186/s12916-024-03617-3.
4
Developmental trajectory and sex differences in auditory processing in a PTEN-deletion model of autism spectrum disorders.自闭症谱系障碍中 PTEN 缺失模型的听觉处理的发育轨迹和性别差异。
Neurobiol Dis. 2024 Oct 1;200:106628. doi: 10.1016/j.nbd.2024.106628. Epub 2024 Aug 5.
5
Adolescent treadmill exercise enhances hippocampal brain-derived neurotrophic factor (BDNF) expression and improves cognition in autism-modeled rats.青少年跑步机运动可增强自闭症模型大鼠海马体中脑源性神经营养因子(BDNF)的表达并改善其认知能力。
Physiol Behav. 2024 Oct 1;284:114638. doi: 10.1016/j.physbeh.2024.114638. Epub 2024 Jul 14.
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The effects of oxytocin administration on social and routinized behaviors in autism: A preregistered systematic review and meta-analysis.催产素给药对自闭症社交和常规行为的影响:一项预注册的系统评价和荟萃分析。
Psychoneuroendocrinology. 2024 Sep;167:107067. doi: 10.1016/j.psyneuen.2024.107067. Epub 2024 May 4.
7
Neonatal immune stimulation results in sex-specific changes in ultrasonic vocalizations but does not affect seizure susceptibility in neonatal mice.新生儿免疫刺激导致超声发声出现性别特异性变化,但不会影响新生小鼠的癫痫易感性。
Int J Dev Neurosci. 2024 Aug;84(5):381-391. doi: 10.1002/jdn.10333. Epub 2024 May 7.
8
The neuroprotective effect of Diosgenin in the rat Valproic acid model of autism.薯蓣皂苷元在丙戊酸致自闭症大鼠模型中的神经保护作用。
Brain Res. 2024 Sep 1;1838:148963. doi: 10.1016/j.brainres.2024.148963. Epub 2024 May 3.
9
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder.自闭症谱系障碍的精神药理学治疗进展
Focus (Am Psychiatr Publ). 2024 Apr;22(2):198-211. doi: 10.1176/appi.focus.24022006. Epub 2024 Apr 10.
10
Oxytocin, GABA, and dopamine interplay in autism.催产素、GABA 和多巴胺在自闭症中相互作用。
Endocr Regul. 2024 Apr 24;58(1):105-114. doi: 10.2478/enr-2024-0012. Print 2024 Jan 1.