EFFECT OF ANTIANDROGENS ON VALPROIC ACID-INDUCED NEURODEVELOPMENTAL CHANGES IN RATS

H. Farghaly, M. Bakr, Hoda E. L. Sayed, I. Ashry
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Abstract

Autism spectrum disorders are a neurodevelopmental condition characterized by disturbances in social interaction and communication, as well as repetitive and restricted behaviors. No efficient treatment plans have been found so far. The neurodevelopmental effects of antiandrogens on developmental milestones were examined in rats following a single intraperitoneal injection of adult pregnant female rats with valproic acid (VPA) (600 mg/kg) on gestation day 12.5. Control females were injected with physiological saline at the same time. The offspring of set 1 (which received physiological saline) was divided into 2 groups (groups 1&2) and the offspring of set 2 (which received VPA) were divided into 5 groups (groups 3-7). Thus, the seven groups were organized as follows: Group 1, the control group in which pups did not receive any treatment. Group 2, pups were given sesame oil vehicle. Group 3 pups did not receive any further treatment. Group 4 in which the pups were given sesame oil. Group 5 in which the pups received 1 mg/day testosterone propionate subcutaneously. Group 6 in which the pups received flutamide 1 mg/kg subcutaneously. Group 7 in which the pups received finasteride 50 mg/kg subcutaneously. Our results demonstrated that VPA-induced retardation in sensorimotor reflexes, but did not affect physical landmarks while antiandrogens improved developmental milestones. In conclusion, our finding confirms that androgen contributes partially towards VPA-induced neurodevelopmental insults.
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抗雄激素对丙戊酸诱导大鼠神经发育变化的影响
自闭症谱系障碍是一种神经发育障碍,其特征是社交互动和沟通障碍,以及重复性和限制性行为。到目前为止还没有找到有效的治疗方案。在妊娠第12.5天,对成年妊娠雌性大鼠单次腹腔注射丙戊酸(VPA) (600 mg/kg),观察抗雄激素对发育里程碑的影响。对照组同时注射生理盐水。将第1组子代(生理盐水组)分为2组(1、2组),第2组子代(VPA组)分为5组(3 ~ 7组)。因此,七个组的组织如下:第一组,对照组,幼鼠不接受任何治疗。第二组,给予香油培养液。第三组幼犬未接受进一步治疗。第4组给幼崽喂香油。第五组:皮下注射丙酸睾酮1 mg/d。第六组给予氟他胺1 mg/kg皮下注射。第7组:皮下注射非那雄胺50 mg/kg。我们的研究结果表明,vpa诱导感觉运动反射的迟缓,但不影响身体标志,而抗雄激素改善发育里程碑。总之,我们的发现证实了雄激素在vpa诱导的神经发育损伤中起部分作用。
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