Luhach Kanishk, Kulkarni Giriraj T, Singh Vijay P, Sharma Bhupesh
Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India.
Department of Pharmaceutics, Gokaraju Rangaraju College of Pharmacy, Hyderabad, India.
J Pharm Pharmacol. 2021 Oct 7;73(11):1460-1469. doi: 10.1093/jpp/rgab115.
Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder, presenting with a variety of aetiological and phenotypical features. Inhibiting the enzyme phosphodiesterase-3 (PDE3) with cilostazol is known to produce beneficial effects in several brain disorders. The pharmacological outcome of cilostazol administration was investigated in prenatal valproic acid (VPA)-induced ASD deficits in albino Wistar rats.
Cilostazol was administered in two doses (30/60 mg/kg) to male rats born of females administered with VPA on gestational day 12. Behavioural assays on locomotion (open field), social interaction, repetitive behaviour (y-maze) and anxiety (elevated plus maze) were performed in all groups. Further, biochemical assessments of markers associated with neuronal function (BDNF, pCREB), inflammation (TNF-α, IL-6, IL-10) and oxidative stress were carried out in frontal cortex, hippocampus, striatum and cerebellum.
The cilostazol regimen, attenuated prenatal VPA exposure associated hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety. Further, biochemical markers such as BDNF, pCREB, IL-10 and GSH were found to be significantly increased contrary to markers such as TNF-α, IL-6 and TBARS in the assessed brain regions.
Cilostazol rectified core behavioural traits while producing significant changes to biochemistry in the brain, suggesting benefits of cilostazol administration in experimental models of ASD.
自闭症谱系障碍（ASD）被归类为一种神经发育障碍，具有多种病因和表型特征。已知用西洛他唑抑制磷酸二酯酶-3（PDE3）酶在几种脑部疾病中会产生有益效果。本研究在白化Wistar大鼠的产前丙戊酸（VPA）诱导的ASD缺陷模型中，研究了西洛他唑给药的药理结果。
在妊娠第12天给雌性大鼠注射VPA，对其雄性后代大鼠以两种剂量（30/60mg/kg）给予西洛他唑。对所有组进行了关于运动（旷场试验）、社交互动、重复行为（Y迷宫试验）和焦虑（高架十字迷宫试验）的行为学测定。此外，还在额叶皮质、海马体、纹状体和小脑中对与神经元功能相关的标志物（脑源性神经营养因子、磷酸化环磷腺苷反应元件结合蛋白）、炎症（肿瘤坏死因子-α、白细胞介素-6、白细胞介素-10）和氧化应激进行了生化评估。
西洛他唑给药方案减轻了产前VPA暴露相关的运动亢进、社交互动缺陷、重复行为和焦虑。此外，在所评估的脑区中，发现脑源性神经营养因子、磷酸化环磷腺苷反应元件结合蛋白、白细胞介素-10和谷胱甘肽等生化标志物显著增加，而肿瘤坏死因子-α、白细胞介素-6和丙二醛等标志物则相反。
西洛他唑纠正了核心行为特征，同时使大脑中的生化指标产生了显著变化，表明西洛他唑给药在ASD实验模型中具有益处。
