Erythropoietin improves neuronal proliferation in dentate gyrus of hippocampal formation in an animal model of Alzheimer's disease

Abstract

Background: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Alzheimer's; erythropoietin; neuronal proliferation; rat; streptozotocin.

Figure 1

Effects of intracerebroventricular injection of streptozotocin (ICV-STZ) on step-through latency in the rats 24 h after the acquisition phase of passive avoidance learning. Data are expressed as mean±SEM (***P<0.001 with respect to the sham group; n=15)

Figure 2

Amount of neuronal proliferation in the granular layer of the hippocampal dentate gyrus of rats with intracerebroventricular injection of streptozotocin after receiving erythropoietin for 2 weeks (n=5, ***P<0.001 in comparison with the control group; †††P<0.001 in comparison with the Alzheimer-erythropoietin[EPO] group)

Figure 3

Photomicrograph of optical microscope from the granular layer of the hippocampal dentate gyrus of rats (a) (M=×4). Ki67-positive cells in the granular layer of the studied groups; control (b), control-erythropoietin (EPO) (c), Alzheimer (d) and Alzheimer-EPO (e) are visible on the arrow tip (M=×40)