Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Unit, University of Karachi, Karachi, Pakistan.
Metab Brain Dis. 2013 Mar;28(1):85-92. doi: 10.1007/s11011-012-9374-y. Epub 2013 Jan 12.
Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.
铅毒性已知会引起广泛的生理、生化和行为功能障碍,可能对包括中枢神经系统在内的多个器官产生不良影响。长期暴露于低水平的铅(Pb(2+))已被证明会通过影响下丘脑-垂体-肾上腺(HPA)轴对啮齿动物和人类产生行为缺陷。这些缺陷被认为与脑单胺神经递质传递的改变有关,并且由于糖皮质激素水平的变化。本研究旨在研究 Pb(2+)暴露对大鼠生长速度、运动活性、焦虑、抑郁、血浆皮质酮和大脑 5-羟色胺(5-HT)水平的影响。大鼠通过饮用水(500ppm;醋酸铅)暴露于铅 5 周。使用强迫游泳试验(FST)评估抑郁。通过高效液相色谱电化学检测测定大脑 5-HT 的估计值。通过分光荧光法测定血浆皮质酮。本研究表明,长期暴露于 Pb(2+)会显著降低 Pb(2+)暴露大鼠的食物摄入量,随后降低生长速度,与对照组相比。Pb(2+)暴露后,开放场活动无明显变化,而焦虑作用明显增加。与对照组相比,Pb(2+)暴露大鼠表现出血浆皮质酮升高和 5-HT 水平降低。与对照组相比,Pb(2+)暴露大鼠表现出明显的抑郁样症状增加。结果在 Pb(2+)诱导大鼠产生应激样反应的背景下进行了讨论,导致血浆皮质酮和大脑 5-HT 水平的变化通过改变色氨酸吡咯酶活性。