Bhanja S, Chainy G B N
Department of Biotechnology, Utkal University, Vani Vihar, Bhubaneswar 751004, India.
Int J Dev Neurosci. 2010 May;28(3):251-62. doi: 10.1016/j.ijdevneu.2010.01.005. Epub 2010 Feb 1.
The objective of the present study was to evaluate the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters, expression of antioxidant defence enzymes, cell proliferation and apoptosis in the developing cerebellum. PTU challenged neonates showed significant decrease in serum T(3) and T(4) levels and marked increase in TSH levels. Significantly elevated levels of cerebellar H(2)O(2) and lipid peroxidation were observed in 7 days old hypothyroid rats, along with increased activities of superoxide dismutase and glutathione peroxidase and decline in catalase activity. In 30 days old hypothyroid rats, a significant decline in cerebellar lipid peroxidation, superoxide dismutase and glutathione peroxidase activity and expression was observed along with an up-regulation in catalase activity and expression. Expression of antioxidant enzymes was studied by Western blot and semi-quantitative rt-PCR. A distinct increase in cell proliferation as indicated by proliferating cell nuclear antigen (PCNA) immunoreactivity was observed in the internal granular layer of cerebellum of 7 days old hypothyroid rats and significant drop in PCNA positive cells in the cerebellar molecular layer and internal granular layer of 30 days old PTU treated rats as compared to controls. In situ end labeling by TUNEL assay showed increased apoptosis in cerebellum of hypothyroid rats in comparison to controls. These results suggest that the antioxidant defence system of the developing cerebellum is sensitive to thyroid hormone deficiency and consequent alterations in oxidative stress status may play a role in regulation of cell proliferation of the cerebellum during neonatal brain development.
本研究的目的是评估6-正丙基硫氧嘧啶（PTU）诱导的甲状腺功能减退对发育中小脑氧化应激参数、抗氧化防御酶表达、细胞增殖和凋亡的影响。接受PTU刺激的新生大鼠血清T(3)和T(4)水平显著降低，TSH水平显著升高。在7日龄甲状腺功能减退大鼠中，观察到小脑H(2)O(2)水平和脂质过氧化显著升高，同时超氧化物歧化酶和谷胱甘肽过氧化物酶活性增加，过氧化氢酶活性下降。在30日龄甲状腺功能减退大鼠中，观察到小脑脂质过氧化、超氧化物歧化酶和谷胱甘肽过氧化物酶活性及表达显著下降，同时过氧化氢酶活性和表达上调。通过蛋白质印迹法和半定量rt-PCR研究抗氧化酶的表达。7日龄甲状腺功能减退大鼠小脑内颗粒层中增殖细胞核抗原（PCNA）免疫反应性显示细胞增殖明显增加，与对照组相比，30日龄PTU处理大鼠小脑分子层和内颗粒层中PCNA阳性细胞显著减少。TUNEL法原位末端标记显示，与对照组相比，甲状腺功能减退大鼠小脑凋亡增加。这些结果表明，发育中小脑的抗氧化防御系统对甲状腺激素缺乏敏感，氧化应激状态的相应改变可能在新生儿脑发育期间小脑细胞增殖的调节中起作用。
