Arabpoor Zohreh, Hamidi Gholamali, Rashidi Bahman, Shabrang Moloud, Alaei Hojjatallah, Sharifi Mohammad Reza, Salami Mahmoud, Dolatabadi Hamid Reza Dehghani, Reisi Parham
Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Adv Biomed Res. 2012;1:50. doi: 10.4103/2277-9175.100157. Epub 2012 Aug 28.
Alzheimer's disease (AD) is a prevalent disorder with severe learning and memory defects. Because it has been demonstrated that erythropoietin (EPO) has positive effects on the central nervous system, the aim of this study was to evaluate the effect of EPO on neuronal proliferation in dentate gyrus of hippocampal formation in a well-defined model for AD.
A rat model of sporadic dementia of Alzheimer's type was established by a bilateral intracerebroventricular injection of streptozotocin (ICV-STZ). Impairment of learning and memory was confirmed 2 weeks after ICV-STZ injection by passive avoidance learning test and then rats were divided into fourgroups:Control, control-EPO, Alzheimer and Alzheimer-EPO. EPO was injected intraperitoneally every other day with a dose of 5000 IU/kg and, finally, the rats were anesthetized and decapitated for immunohistochemical study and neurogenesis investigation (by Ki67 method) in dentate gyrus of hippocampal formation.
The results driven from the histological study showed that EPO significantly increases neuronal proliferation in dentate gyrus of hippocampus in the Alzheimer-EPO group compared with the control, control-EPO and Alzheimer groups; however, there were no differences between the other groups.
Our results show that even though EPO in intact animals doesnot change neurogenesis in dentate gyrus, it can nonetheless significantly increase neurogenesis if there is an underlying disorder like neurodegenerative diseases.
阿尔茨海默病(AD)是一种常见的具有严重学习和记忆缺陷的疾病。由于已证明促红细胞生成素(EPO)对中枢神经系统有积极作用,本研究的目的是在一个明确的AD模型中评估EPO对海马结构齿状回神经元增殖的影响。
通过双侧脑室内注射链脲佐菌素(ICV-STZ)建立散发性阿尔茨海默型痴呆大鼠模型。在ICV-STZ注射2周后,通过被动回避学习试验确认学习和记忆受损,然后将大鼠分为四组:对照组、对照-EPO组、阿尔茨海默病组和阿尔茨海默病-EPO组。每隔一天腹腔注射EPO,剂量为5000 IU/kg,最后,将大鼠麻醉并处死,用于海马结构齿状回的免疫组织化学研究和神经发生调查(采用Ki67法)。
组织学研究结果表明,与对照组、对照-EPO组和阿尔茨海默病组相比,阿尔茨海默病-EPO组中EPO显著增加了海马齿状回的神经元增殖;然而,其他组之间没有差异。
我们的结果表明,即使在完整动物中EPO不会改变齿状回的神经发生,但如果存在像神经退行性疾病这样的潜在疾病,它仍能显著增加神经发生。