title: Neuroprotective effects of erythropoietin on Alzheimer's dementia model in rats.
abstract: BACKGROUND
  Although Alzheimer's disease (AD) is the most common age-related neurodegenerative disease and characterized by memory impairment, only symptomatic treatments are available.
  
  
  OBJECTIVE
  Because recombinant human erythropoietin (rhEPO) has various neuroprotective effects and improves cognitive function in animal models of neurodegenerative disorders, we investigated the therapeutic effects of rhEPO in an intracerebroventricular (ICV)-streptozotocin (STZ) animal model of sporadic-AD.
  
  
  METHODS
  A total of 24 Sprague-Dawley adult rats were divided into 4 groups of naive control (n = 6), sham-operated (n = 6), ICV-STZ + saline (n = 6) and ICV-STZ + rhEPO (n = 6). Twelve rats with Alzheimer's disease, induced by STZ injection (3 mg/kg) into both lateral ventricles using a stereotaxic frame (bilaterally ICV-STZ), were divided into 2 groups 5 days after the STZ injection: one treated with rhEPO 5000 (IU/kg/day, i.p.) and the other with 0.9% NaCl (1 mL/kg/day, i.p.) for 2 weeks. The sham-operated rats received bilaterally ICV-0.9% NaCl. No surgical operation or treatment was given to the naive-control animals. On day 20, a passive avoidance learning (PAL) test was used followed by sacrification and removal of the brain tissue in all animals. Brain TNF-α and ChAT levels were determined, and neurons in the hippocampal CA1 and CA3 regions were counted by Cresyl violet staining.
  
  
  RESULTS
  ICV-STZ was found to significantly shorten the latency time on the PAL, increase brain TNF-α level, and decrease brain ChAT activity and the number of neurons in the hippocampal CA1 and CA3 regions. On the other hand, rhEPO significantly attenuated all these detrimental effects induced by STZ.
  
  
  CONCLUSIONS
  RhEPO treatment significantly prevented the ICV-STZ-induced memory deficit by attenuating the hippocampal neuronal loss, neuroinflammation and cholinergic deficit in rats. This result suggests that rhEPO may be beneficial for treating AD.
authors.affiliation: Department of Neurology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey.
authors.forename: Betul
authors.initials: B
authors.lastname: Cevik
authors.affiliation: Department of Neurology, Turhal State Hospital, Tokat, Turkey.
authors.forename: Volkan
authors.initials: V
authors.lastname: Solmaz
authors.affiliation: Department of Histology and Embryology, Ege University, Faculty of Medicine, Izmir, Turkey.
authors.forename: Gurkan
authors.initials: G
authors.lastname: Yigitturk
authors.affiliation: Department of Histology and Embryology, Ege University, Faculty of Medicine, Izmir, Turkey.
authors.forename: Turker
authors.initials: T
authors.lastname: Cavusoğlu
authors.affiliation: Department of Physiology, Ege University, Faculty of Medicine, Izmir, Turkey.
authors.forename: Gonul
authors.initials: G
authors.lastname: Peker
authors.affiliation: Department of Physiology, Istanbul Bilim University, Faculty of Medicine, Istanbul, Turkey.
authors.forename: Oytun
authors.initials: O
authors.lastname: Erbas
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C554270:EPO protein, human; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin
keywords: Alzheimer’s disease; erythropoietin; hippocampus; neuroprotection; streptozotocin