Vakili Shahrbabaki Seyyed Sajjad, Jonaidi Hossein, Sheibani Vahid, Bashiri Hamideh
Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran; Department of Biology, University of Turku, Turku 20014, Finland.
Division of Physiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.
Physiol Behav. 2022 May 15;249:113739. doi: 10.1016/j.physbeh.2022.113739. Epub 2022 Feb 11.
Early life events are known to greatly affect brain development, cortical neurogenesis, and Hypothalamic-pituitary-adrenal activity. Mainly characterized by impairment in social communication, language, and cognitive development, autism spectrum disorder (ASD) refers to a class of neuropsychiatric disorders with numerous genetic and environmental risk factors. In the early handling (EH) method, daily separation of infants from their mother, physical touching, and exposure to a new environment occur. Here, we studied the effect of EH on Social interaction, learning, and memory in rats exposed pre-or post-natally to valproic acid (VPA). Gestational VPA exposure (600 mg/kg) led to some severe autistic-like traits, more notable in the social behavior of the male sex, along with unchanged to partially altered spatial learning and memory function and reduced avoidance memory. In comparison, while causing a sex-dependent increase in spatial memory, subcutaneous injection of VPA (400 mg/kg) in infancy resulted in limited adverse autistic features, including a decrease in males' social preference, as well as reduced avoidance memory. The results indicated that neonatal handling significantly improved multiple social behavior and memory deficits in prenatally injected rats. In contrast, EH in rats receiving postnatal VPA elicited a restricted advantage on social novelty tendency; while negatively affecting some other social behavior criteria and spatial learning of males and encouraging sex-dependent repetitive behaviors in the social setting. The controversial influence of postnatal handling on juvenile rats of postnatal VPA treatment vs. prenatal VPA treatment opens up the potential for future research on the context-based consequence of early-life handling stress using different behavioral tasks and to benefit therapeutic procedures through understanding the sex- and age-specific neurobiology of short-term environmental manipulation in animal models of autism.
已知早期生活事件会极大地影响大脑发育、皮质神经发生以及下丘脑 - 垂体 - 肾上腺活动。自闭症谱系障碍（ASD）主要表现为社交沟通、语言和认知发展受损，是一类具有众多遗传和环境风险因素的神经精神疾病。在早期处理（EH）方法中，婴儿会每日与母亲分离、接受身体接触并接触新环境。在此，我们研究了EH对产前或产后暴露于丙戊酸（VPA）的大鼠的社交互动、学习和记忆的影响。孕期暴露于VPA（600mg/kg）会导致一些严重的自闭症样特征，在雄性的社交行为中更为明显，同时空间学习和记忆功能未改变或部分改变，回避记忆减少。相比之下，婴儿期皮下注射VPA（400mg/kg）虽然会导致空间记忆出现性别依赖性增加，但只会产生有限的不良自闭症特征，包括雄性社交偏好降低以及回避记忆减少。结果表明，新生期处理显著改善了产前注射VPA大鼠的多种社交行为和记忆缺陷。相比之下，产后接受VPA的大鼠进行EH对社交新奇倾向产生的优势有限；同时对雄性的其他一些社交行为标准和空间学习产生负面影响，并在社交环境中引发性别依赖性重复行为。产后处理对产后VPA治疗的幼鼠与产前VPA治疗的幼鼠的影响存在争议，这为未来研究利用不同行为任务探究早期生活处理应激基于背景的后果以及通过了解自闭症动物模型中短期环境操纵的性别和年龄特异性神经生物学来改进治疗程序开辟了潜力。
