Kacimi Fatima Ezzahra, Esselmani Hicham, Ed-Day Soumia, Nechchadi Habiba, Merzouki Mohamed, Ramchoun Mhamed, Azzaoui Fatima-Zahra, Boulbaroud Samira
Biotechnology and Sustainable Development of Natural Resources Unit, Polydisciplinary Faculty, Sultan Moulay Slimane University, Beni Mellal, Morocco.
Biological Engineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, Beni Mellal, Morocco.
J Mol Histol. 2025 Aug 8;56(4):258. doi: 10.1007/s10735-025-10553-w.
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social deficits, repetitive behaviors, and cognitive impairments. Evidence suggests that Vitamin A deficiency (VAD) may exacerbate ASD-related abnormalities, while Vitamin A supplementation (VAS) may offer neuroprotection. This study investigates the effects of Vitamin A modulation on neuronal integrity, cognitive function, and social behavior in a valproic acid (VPA)-induced ASD rat model, focusing on histological changes, behavioral outcomes, and serum Vitamin A levels. Pregnant Wistar rats received VPA (500 mg/kg) on gestational day 12.5. Offspring were divided into Control, VPA, VAD, VPA + VAD, and VPA + VAS (2000 IU/kg diet) groups. Serum Vitamin A levels were quantified using spectrophotometry. Histopathological analysis of the hippocampus, cerebellum, and prefrontal cortex (PFC) assessed neuronal and glial cell densities. Behavioral tests included the Three-Chamber Social Interaction Test for sociability and the Novel Object Recognition Test for memory function. Serum analysis showed significantly lower Vitamin A levels in VAD and VPA + VAD groups, while VAS restored levels. Histological analysis revealed reduced neuronal density and increased glial activation in VPA, VAD, and VPA + VAD groups. The VPA + VAS group exhibited partial neuronal recovery. Behaviorally, VAS improved sociability and memory performance, correlating with neuronal preservation. These findings suggest that Vitamin A deficiency worsens ASD-related impairments, while supplementation restores neuronal integrity and cognitive function, highlighting its potential therapeutic role in ASD.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征为社交缺陷、重复行为和认知障碍。有证据表明，维生素A缺乏（VAD）可能会加剧与ASD相关的异常情况，而补充维生素A（VAS）可能具有神经保护作用。本研究调查了在丙戊酸（VPA）诱导的ASD大鼠模型中，维生素A调节对神经元完整性、认知功能和社交行为的影响，重点关注组织学变化、行为结果和血清维生素A水平。妊娠第12.5天，怀孕的Wistar大鼠接受VPA（500mg/kg）。后代分为对照组、VPA组、VAD组、VPA+VAD组和VPA+VAS组（饮食中添加2000IU/kg）。使用分光光度法定量血清维生素A水平。对海马体、小脑和前额叶皮质（PFC）进行组织病理学分析，评估神经元和胶质细胞密度。行为测试包括用于社交能力的三室社交互动测试和用于记忆功能的新物体识别测试。血清分析显示，VAD组和VPA+VAD组的维生素A水平显著降低，而VAS使水平恢复。组织学分析显示，VPA组、VAD组和VPA+VAD组的神经元密度降低，胶质细胞激活增加。VPA+VAS组表现出部分神经元恢复。在行为方面，VAS改善了社交能力和记忆表现，这与神经元的保存相关。这些发现表明，维生素A缺乏会加重与ASD相关的损伤，而补充维生素A可恢复神经元完整性和认知功能，凸显了其在ASD中的潜在治疗作用。
