Adıgüzel Emre, Bozkurt Nuh Mehmet, Ünal Gökhan, Waszkiewicz Napoleon
Department of Nutrition and Dietetics, Faculty of Health Sciences, Karamanoğlu Mehmetbey University, 70100 Karaman, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Erciyes University, 38280 Kayseri, Turkey.
Biology (Basel). 2025 Aug 16;14(8):1065. doi: 10.3390/biology14081065.
: Autism spectrum disorder is a psychological condition characterized by symptoms such as repetitive stereotypic behaviors and social interaction/communication difficulties. It is known that omega-3 deficiency during brain maturation may cause learning disabilities and motor impairment. Therefore, we examined the effects of omega-3 treatment during gestation and/or lactation on autism-related behavioral and molecular deficits in a valproic acid (VPA)-rat model. : Female Wistar rats were divided into five groups: control, VPA (500 mg/kg at G12.5), VPA+omega-3 (gestation), VPA+omega-3 (lactation), and VPA+omega-3 (gestation + lactation). The omega-3 supplement was dissolved in drinking water and offered for consumption daily during gestation and/or lactation. After the treatment period, behavioral tests were performed. The rats were then sacrificed, and inflammatory cytokines, parvalbumin, and glutamate decarboxylase-67 (GAD67) levels in the prefrontal cortex and hippocampus were examined. : Prenatal VPA administration increased repetitive behaviors, decreased sociability, impaired memory, and induced anhedonia. The behavioral and neurochemical effects of VPA exposure were more severe in males than in females. Early maternal omega-3 treatments rescued these behavioral changes. The treatments also reversed prenatal VPA-induced neuroinflammation. Lastly, GAD67 and parvalbumin decreases in these brain regions were mitigated by the treatments, the therapeutic effects of which were more pronounced in males. In terms of efficacy, the treatment groups ranked as follows: "gestation + lactation" > "gestation" > "lactation". : Maternal omega-3 supplementation-especially when administered throughout gestation and lactation-provides significant protection against behavioral and neurochemical deficits associated with prenatal VPA exposure. Early omega-3 intake may serve as a valuable complementary strategy in autism intervention.
自闭症谱系障碍是一种心理状况，其特征包括重复刻板行为以及社交互动/沟通困难等症状。众所周知，大脑发育过程中ω-3缺乏可能导致学习障碍和运动功能受损。因此，我们研究了在孕期和/或哺乳期进行ω-3治疗对丙戊酸（VPA）诱导的大鼠自闭症相关行为和分子缺陷的影响。雌性Wistar大鼠分为五组：对照组、VPA组（妊娠12.5天时给予500mg/kg）、VPA+ω-3（孕期）组、VPA+ω-3（哺乳期）组和VPA+ω-3（孕期+哺乳期）组。ω-3补充剂溶解于饮用水中，在孕期和/或哺乳期每日供大鼠饮用。治疗期结束后，进行行为测试。然后处死大鼠，检测前额叶皮质和海马体中的炎性细胞因子、小白蛋白以及谷氨酸脱羧酶67（GAD67）水平。产前给予VPA增加了重复行为，降低了社交能力，损害了记忆力，并诱发了快感缺失。VPA暴露对行为和神经化学的影响在雄性大鼠中比雌性大鼠更严重。早期母体ω-3治疗挽救了这些行为变化。这些治疗还逆转了产前VPA诱导的神经炎症。最后，这些脑区中GAD67和小白蛋白的减少通过治疗得到缓解，其治疗效果在雄性大鼠中更明显。在疗效方面，治疗组排名如下：“孕期+哺乳期”>“孕期”>“哺乳期”。母体补充ω-3——尤其是在整个孕期和哺乳期进行补充——可显著预防与产前VPA暴露相关的行为和神经化学缺陷。早期摄入ω-3可能是自闭症干预中有价值的补充策略。
