Sever I H, Ozkul B, Bozkurt M F, Erbas O
Demiroglu Bilim University, School of Medicine, Department of Radiology, Istanbul, Turkey.
Istanbul Atlas University, School of Medicine, Department of Radiology, Istanbul, Turkey.
Neurosci Lett. 2022 May 14;779:136622. doi: 10.1016/j.neulet.2022.136622. Epub 2022 Apr 7.
Autism is a clinically defined neurodevelopmental disorder with unknown origin characterized by significant social, communication and behavioral challenges. Although it can be a lifelong condition, treatments can help alleviate symptoms and enhance a patient's quality of life.
We aimed to assess the therapeutic potential of finasteride in autism with biochemical markers, histopathological evaluation, behavioral tests and radiological imaging.
Propionic acid (PPA) was injected intraperitoneally into 20 out of 30 rats for 5 days to establish an autism model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 10), placebo group (intraperitoneal PPA + 1 ml/kg/day % 0.9 NaCl saline was given via oral gavage for 15 days, n = 10) and treated group (intraperitoneal PPA + 5 mg/kg/day of finasteride was given via oral gavage for 15 days, n = 10). After 4 days of behavioral tests, magnetic resonance spectroscopy (MRS) was performed for measuring creatine and lactate levels. All animals were sacrificed for histopathological examination and biochemical analysis of brain tissue.
MDA, NFκB, TNF-α, IL-2, IL-17A and lactate levels in brain homogenates were significantly increased in the placebo group compared to the control group, while Nfr2 levels were decreased; and the levels of all biochemical markers were reversed by finasteride treatment. A significant improvement was observed in autism-like behaviors in rats treated with finasteride compared to the placebo group. Further, the creatine and lactate levels in corpus striatum in MRS, the neuronal counts and glial activity of the hippocampus and cerebellum were closer to the control group in the finasteride-treated group compared to the placebo group.
Finasteride led significant improvement in autism-like symptoms with its antioxidant effect through Nrf2 modulation in addition to its anti androgen effect.
自闭症是一种临床定义的神经发育障碍，病因不明，其特征是存在显著的社交、沟通和行为挑战。尽管它可能是一种终身疾病，但治疗有助于缓解症状并提高患者的生活质量。
我们旨在通过生化标志物、组织病理学评估、行为测试和放射影像学来评估非那雄胺在自闭症治疗中的潜力。
将30只大鼠中的20只腹腔注射丙酸（PPA），持续5天以建立自闭症模型。大鼠被随机分为四组：对照组（未进行任何处理，n = 10）、安慰剂组（腹腔注射PPA + 每天1 ml/kg的0.9%氯化钠盐水经口灌胃15天，n = 10）和治疗组（腹腔注射PPA + 每天5 mg/kg的非那雄胺经口灌胃15天，n = 10）。在进行4天的行为测试后，进行磁共振波谱（MRS）以测量肌酸和乳酸水平。所有动物均处死后进行脑组织的组织病理学检查和生化分析。
与对照组相比，安慰剂组脑匀浆中的丙二醛（MDA）、核因子κB（NFκB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）、白细胞介素-17A（IL-17A）和乳酸水平显著升高，而核因子E2相关因子2（Nfr2）水平降低；非那雄胺治疗使所有生化标志物的水平恢复正常。与安慰剂组相比，非那雄胺治疗的大鼠自闭症样行为有显著改善。此外，与安慰剂组相比，非那雄胺治疗组MRS纹状体中的肌酸和乳酸水平、海马和小脑的神经元计数及神经胶质细胞活性更接近对照组。
非那雄胺除具有抗雄激素作用外，还通过调节Nrf2发挥抗氧化作用，从而显著改善自闭症样症状。
