Gene expression alterations in brain areas of intracerebroventricular streptozotocin treated rat.
Gene expression alterations in brain areas of intracerebroventricular streptozotocin treated rat.
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DOI：
10.3233/jad-2006-9305
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
E. Grünblatt;E. Koutsilieri;S. Hoyer;P. Riederer
中科院分区：
文献类型：
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作者：
E. Grünblatt;E. Koutsilieri;S. Hoyer;P. Riederer
链脲佐菌素外周注射是实验性糖尿病的诱因。然而，当在脑室内注射链脲佐菌素时，在认知功能、进食、伤害性感觉、大脑葡萄糖代谢、神经传递和氧化应激方面，链脲佐菌素显示出一整套特定的生化和行为变化，而不会产生动脉高血糖，类似于阿尔茨海默病。为了揭示链脲佐菌素致大鼠神经退行性变的作用机制，我们采用实时荧光定量RT-PCR方法，研究了炎症、氧化应激、生长因子和转录因子在大脑皮层、纹状体和小脑中的表达。链脲佐菌素处理组大鼠大脑皮质GDNF、BDNF和整合素α-M基因表达上调，而即刻早期基因转录因子NGF-IB和金属硫蛋白-1/2表达下调。相反，NGF-IB、GDNF和BDNF在纹状体和小脑中的表达没有改变。而整合素α-M和金属硫蛋白-1/2在纹状体表达显著减少，在小脑表达增加。这些基因的变化可能为深入了解神经元胰岛素信号转导受抑后的一连串生理异常提供线索。此外，与散发性阿尔茨海默病的神经细胞死亡相似之处可能会变得明显。
Streptozotocin is well known inducer of experimental diabetes mellitus when injected peripherally. However, when administered intracerebroventricular, streptozotocin showed a whole spectrum of specific biochemical and behavioural alterations with regard to cognitive functions, feeding, nociception, brain glucose metabolism, neurotransmission and oxidative stress, without producing arterial hyperglycaemia, similarly to Alzheimer's disease. In order to reveal the mechanism of action of neurodegeneration in streptozotocin rat model we investigated the expression of several genes involved in inflammation, oxidative stress, growth- and transcription-factors in the cortex, striatum and cerebellum, using real-time quantitative RT-PCR. Genes such as GDNF, BDNF and integrin-alpha-M were up-regulated, while immediate-early-gene-transcription-factor NGF-IB and metallothionein-1/2 were down-regulated in the cortex of streptozotocin-treated rats. Conversely, NGF-IB, GDNF and BDNF mRNA expression did not alter in the striatum and cerebellum. However, integrin alpha-M and metallothionein-1/2 expressions decreased significantly in the striatum and increased in the cerebellum. These gene changes may provide an insight into the cascade of physiological abnormalities following the inhibition of neuronal insulin signal transduction. Additionally, similarities to neuronal cell death in sporadic Alzheimer's disease may become apparent.