Pragnya B, Kameshwari J S L, Veeresh B
Department of Pharmacology, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad, Andhra Pradesh 500027, India.
Department of Pharmacology, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad, Andhra Pradesh 500027, India.
Behav Brain Res. 2014 Aug 15;270:86-94. doi: 10.1016/j.bbr.2014.04.045. Epub 2014 May 5.
Post natal exposure to VPA (valproic acid) in mice induces behavioral deficits, abnormal sensitivity to sensory stimuli and self-injurious behavior, observed in autism. Piperine has been reported to have protective effect on brain. The present study aimed at evaluating effect of piperine on VPA induced neurobehavioral and biochemical alterations in BALB/c mice. Young BALB/c mice 13 days old were procured from five different litters and segregated into five groups (n=6; 3 male, 3 female) i.e., Group I served as control group, received physiological saline on PND (Post natal day) 14 & Tween 80 p.o. from PND13-40. Group II served as normal treated group and received piperine (20mg/kg p.o.) from PND 13-40 and saline s.c. on PND 14. Group III served as valproate treated group received VPA (400mg/kg s.c.) on PND 14 and Tween 80 p.o. from PND 13-40. Group IV & V served as disease treated group received VPA (400mg/kg s.c.) on PND 14 & piperine (5 & 20mg/kg p.o.) from PND 13-40 respectively. BALB/c mice pups were subjected to behavioral testing to assess motor skill development, nociceptive response, locomotion, anxiety, and cognition on various postnatal days up to PND 40. At the end of behavioral evaluation, mice were sacrificed; brain was isolated for biochemical estimations (serotonin, glutathione, MDA and nitric oxide) and histopathological examination. Our study revealed that treatment with piperine significantly improved behavioral alterations, lowered oxidative stress markers, and restored histoarchitecture of cerebellum. This ameliorating effect of piperine is attributed to its anti-oxidant activity, cognition enhancing and neuroprotective activity.
小鼠出生后暴露于丙戊酸(VPA)会引发行为缺陷、对感觉刺激的异常敏感性以及自伤行为,这些都是自闭症中会出现的症状。据报道,胡椒碱对大脑具有保护作用。本研究旨在评估胡椒碱对VPA诱导的BALB/c小鼠神经行为和生化改变的影响。从五个不同的窝中获取13日龄的年轻BALB/c小鼠,并将其分为五组(n = 6;3只雄性,3只雌性),即:第一组作为对照组,在出生后第14天接受生理盐水,并从出生后第13天至40天口服吐温80。第二组作为正常治疗组,从出生后第13天至40天接受胡椒碱(20mg/kg口服),并在出生后第14天皮下注射生理盐水。第三组作为丙戊酸盐治疗组,在出生后第14天接受VPA(400mg/kg皮下注射),并从出生后第13天至40天口服吐温80。第四组和第五组作为疾病治疗组,分别在出生后第14天接受VPA(400mg/kg皮下注射),并从出生后第13天至40天接受胡椒碱(5mg/kg和20mg/kg口服)。对BALB/c小鼠幼崽进行行为测试,以评估其在出生后直至第40天的不同时间点的运动技能发育、伤害性反应、运动能力、焦虑和认知情况。在行为评估结束时,处死小鼠;分离大脑进行生化指标测定(血清素、谷胱甘肽、丙二醛和一氧化氮)以及组织病理学检查。我们的研究表明,胡椒碱治疗可显著改善行为改变,降低氧化应激标志物水平,并恢复小脑的组织结构。胡椒碱的这种改善作用归因于其抗氧化活性、认知增强和神经保护活性。