Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Director AIIMS Bhopal and Chairman RIC, ISF College of Pharmacy, Moga, Punjab, 142001, India.
Neurotox Res. 2020 Apr;37(4):815-826. doi: 10.1007/s12640-020-00169-1. Epub 2020 Feb 5.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by restrictive behaviour, deficit in social skills and interaction. The multifactorial etiology, complex pathophysiology and different combination of symptoms (unusual speech patterns, frequent repetition of phrases) make it difficult to treat. Thus, present study aimed to find the protective effects of oxiracetam alone and in combination with zinc on brain behavioral, biochemical, pro-inflammatory cytokines and neurotransmitters level. Rats were administered with propionic acid (250 mg/kg p.o.) for 3 days and immediately on next day treatment were given with oxiracetam (25, 50 mg/kg i.p), zinc (4 mg/kg) as well as oxiracetam (25 mg/kg i.p) in combination with zinc (4 mg/kg p.o). Behavioral parameters were performed from 22th to 28th day. On 29th day, all the animals were sacrificed by cervical dislocation and the brain was preserved for biochemical (LPO, GSH, nitrite, mitochondrial complex I, IV and cAMP), neuroinflammatory (TNF-α, IL-1β, IL-6) and neurotransmitters (5-HT, GABA, glutamate and acetylcholine) analysis. The propionic acid administration showed memory impairment, restrictive behavior, increased proinflammatory cytokines level, biochemical and neurotransmitters alteration. However, treatment with oxiracetam alone and in combination with zinc significantly attenuated behavioral, biochemical, inflammatory cytokines and restored neurotransmitters level. The finding of present study demonstrated that oxiracetam alone and in combination with zinc afforded superior anti-autistic effect through antioxidant, anti-inflammatory and anti-excitotoxic mechanisms and could serve as attractive strategy in managing autism.
自闭症谱系障碍（ASD）是一种复杂的神经发育障碍，其特征为行为受限、社交技能和互动缺陷。其多因素病因、复杂的病理生理学以及不同症状的组合（异常的言语模式、频繁重复短语）使其难以治疗。因此，本研究旨在寻找单独使用和联合使用奥拉西坦以及锌对大脑行为、生化、促炎细胞因子和神经递质水平的保护作用。大鼠连续 3 天给予丙戊酸（250mg/kg，po），第 2 天立即给予奥拉西坦（25、50mg/kg，ip）、锌（4mg/kg）以及奥拉西坦（25mg/kg，ip）联合锌（4mg/kg，po）。从第 22 天到第 28 天进行行为参数测试。第 29 天，所有动物通过颈椎脱位处死，保存大脑用于生化（LPO、GSH、亚硝酸盐、线粒体复合物 I、IV 和 cAMP）、神经炎症（TNF-α、IL-1β、IL-6）和神经递质（5-HT、GABA、谷氨酸和乙酰胆碱）分析。丙戊酸给药导致记忆障碍、行为受限、促炎细胞因子水平升高、生化和神经递质改变。然而，单独使用奥拉西坦和联合使用锌可显著减轻行为、生化、炎症细胞因子并恢复神经递质水平。本研究的结果表明，奥拉西坦单独和联合使用锌通过抗氧化、抗炎和抗兴奋毒性机制发挥出优越的抗自闭症作用，并可能成为管理自闭症的有吸引力的策略。
