Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan.
Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan.
Life Sci. 2015 Mar 1;124:110-9. doi: 10.1016/j.lfs.2015.01.016. Epub 2015 Jan 28.
D-Galactose (D-gal) induced accelerated senescence has been used to develop an aging model for brain. Previously, long term administration of a wide range of doses has been used for this purpose. In the present study we investigate whether short term administration of a high dose of D-gal in rats induces significant signs and symptoms similar to natural aging.
Young rats were injected intraperitoneally with D-gal at a dose of 300 mg/ml/kg for one week. Behavioral analysis for depression and anxiety like symptoms were monitored by forced swim test (FST) and light/dark transition (LDT) test. Assessment of memory was done using the Morris water maze (MWM), passive avoidance test (PAT) and elevated plus maze (EPM) test. Biochemical analysis was done for estimation of antioxidant enzymes and acetylcholinesterase. Determination of brain biogenic amines was performed by HPLC-EC.
Short term administration of D-gal significantly altered behavioral, biochemical and neurochemical responses in rats. D-Gal injected rats exhibited depressogenic and anxiogenic behaviors while memory was also significantly impaired in these rats. Brain lipid peroxidation and superoxide dismutase activity were significantly increased while catalase and glutathione peroxidase decreased. Increased activity of acetylcholinesterase was also exhibited by D-gal injected rats while brain biogenic amines were significantly decreased. Food intake and growth rate were however comparable in both groups.
Together the behavioral, biochemical and neurochemical impairments following the high dose of D-gal suggest that symptoms similar to natural aging may be developed in rats in as early as one week.
D-半乳糖（D-gal）诱导的加速衰老已被用于开发大脑衰老模型。此前，为达到此目的，已使用了广泛剂量的长期给药。在本研究中，我们研究了在大鼠中短期给予高剂量 D-gal 是否会引起与自然衰老相似的显著症状和体征。
年轻大鼠腹腔内注射 D-gal 剂量为 300mg/ml/kg，持续一周。采用强迫游泳试验（FST）和明暗交替试验（LDT）监测抑郁和焦虑样症状的行为分析。通过 Morris 水迷宫（MWM）、被动回避试验（PAT）和高架十字迷宫（EPM）试验评估记忆。采用生化分析测定抗氧化酶和乙酰胆碱酯酶。通过 HPLC-EC 测定脑生物胺。
短期给予 D-gal 可显著改变大鼠的行为、生化和神经化学反应。D-gal 注射大鼠表现出抑郁和焦虑行为，而这些大鼠的记忆也明显受损。脑脂质过氧化和超氧化物歧化酶活性显著增加，而过氧化氢酶和谷胱甘肽过氧化物酶活性降低。D-gal 注射大鼠还表现出乙酰胆碱酯酶活性增加，而脑生物胺显著减少。然而，两组的食物摄入量和生长速度相当。
D-gal 高剂量后出现的行为、生化和神经化学损伤表明，大鼠在短短一周内可能会出现类似于自然衰老的症状。
