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.

The Promises and Challenges of Erythropoietin for Treatment of Alzheimer’s Disease

“…Moreover, EPO promotes survival of septal cholinergic neurons in adult rats which have undergone fimbria-fornix transections (Konishi et al 1993). Intraperitoneal administration of EPO spurs significant neurogenesis in the dentate gyrus in the streptozotocin-induced AD rat model; however, EPO does not change neurogenesis in the dentate gyrus of intact animals (Arabpoor et al 2012). Tg2576 mice treated with EPO show increased hippocampal and cortical neurogenesis identified by 5bromo-2-deoxyuridine fluorescent labeling, and increased synaptophysin expression.…”

“…T. Lee et al 2012;Y. P. Li et al 2015;Armand-Ugon et al 2015;Samy et al 2016;Arabpoor et al 2012). Systemic routes, though less invasive than the intracranial or intracerebroventricular routes used to bypass the BBB, require high dosage to infiltrate the brain and therefore result in heightened peripheral toxicity risk.…”

Neuroprotective effects of EpoL against oxidative stress induced by soluble oligomers of Aβ peptide

“…These results correlate with an increase in cognitive function, as evaluated by the Morris water maze test [11]. Additionally, Epo treatment has been associated with stimulation of neuronal proliferation in the dentate gyrus of the hippocampus in an AD animal model [12,13]. These data correlate with results that show an increase in EpoR expression in brain lysates from Alzheimer's patients as compared to brain lysates of healthy patients [14].…”

Effect of cholecystokinin on learning and memory, neuronal proliferation and apoptosis in the rat hippocampus

“…Studies have shown that programmed cell death or apoptosis exists in the central nervous system of adult mammalian and this programmed cell death often presents in the area where neurogenesis is seen even in adulthood; like DG of hippocampal formation. [ 13 ] Since a very high number of new neurons are made during adult neurogenesis and only some of them survive, and others encounter apoptosis,[ 14 ] therefore it has been suggested that apoptosis is actually dependent on neurogenesis. [ 15 ] In the hippocampus, neural progenitors in the subgranular zone of the DG proliferate, and the new neurons migrate to the DG granular layer and participate in the building of hippocampal neuronal circuits.…”