Mirzaee Khoram-Abadi Khadijeh, Haratizadeh Sara, Basiri Mohsen, Parvan Mahdieh, Pourjafari Fahimeh, Aghaei Iraj, Amiresmaili Sedigheh, Nozari Masoumeh
Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Iran J Basic Med Sci. 2024;27(3):335-342. doi: 10.22038/IJBMS.2023.74536.16190.
Due to the crucial role of polyamines during fetal growth and development, we aimed to determine the effect of prenatal administration of agmatine, an endogenous active metabolite of arginine, and a nutritional supplement, on autistic-like behaviors, oxidative-anti-oxidative profile, and histopathological changes of the prefrontal cortex (PFC) and CA1 area of the hippocampus in valproic acid (VPA) model of autism in male rats.
VPA was injected intraperitoneally on embryonic days (ED) 12.5, and the pregnant rats were gavaged with agmatine between E6.5 to E18.5 (13 days), at doses of 0.001, 0.01, and 0.1 mg/kg. The autism-like behaviors and memory of male pups were analyzed via open-field, three-chamber, and novel object recognition tests. Serum oxidative stress and the histological changes in the PFC and CA1 were assessed at the end of the study.
The results suggest that prenatal agmatine reduced autistic-like behaviors by decreasing cell loss in CA1 and PFC. We observed no alterations in superoxide dismutase (SOD) level and total anti-oxidant capacity (TAC) between groups. VPA decreased catalase (CAT) activities, while agmatine decreased malondialdehyde (MDA) activity.
Overall, this investigation suggests that agmatine may be a potential candidate for the early treatment and even prevention of appearance of autism symptoms.
由于多胺在胎儿生长发育过程中起着关键作用,我们旨在确定产前给予精胺(精氨酸的一种内源性活性代谢产物及营养补充剂)对雄性大鼠丙戊酸(VPA)自闭症模型中自闭症样行为、氧化-抗氧化状态以及前额叶皮质(PFC)和海马CA1区组织病理学变化的影响。
在胚胎第12.5天腹腔注射VPA,并在胚胎第6.5天至第18.5天(共13天)期间,以0.001、0.01和0.1mg/kg的剂量给怀孕大鼠灌胃精胺。通过旷场试验、三室试验和新物体识别试验分析雄性幼崽的自闭症样行为和记忆。在研究结束时评估血清氧化应激以及PFC和CA1区的组织学变化。
结果表明,产前给予精胺可通过减少CA1区和PFC区的细胞损失来降低自闭症样行为。我们观察到各组之间超氧化物歧化酶(SOD)水平和总抗氧化能力(TAC)没有改变。VPA降低了过氧化氢酶(CAT)活性,而精胺降低了丙二醛(MDA)活性。
总体而言,本研究表明精胺可能是早期治疗甚至预防自闭症症状出现的潜在候选物。