Effect of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) on learning and memory impairment and hippocampal apoptosis induced by intracerebroventricular administration of streptozotocin in rats.
Alzheimer Disease
/ chemically induced
Animals
Antibiotics, Antineoplastic
/ toxicity
Apoptosis
/ drug effects
Behavior, Animal
/ drug effects
Brain
/ drug effects
Caspase 3
/ metabolism
Disease Models, Animal
Erythropoietin
/ analogs & derivatives
Hippocampus
/ drug effects
Immunoglobulin Fc Fragments
/ pharmacology
Injections, Intraventricular
Learning
/ drug effects
Memory
/ drug effects
Morris Water Maze Test
Neuroprotective Agents
/ pharmacology
Rats
Recombinant Fusion Proteins
/ pharmacology
Streptozocin
/ toxicity
Alzheimer’s disease
Apoptosis
Carbamylated erythropoietin
Hippocampus
Memory
Rat
Streptozotocin
Journal
Behavioural brain research
ISSN: 1872-7549
Titre abrégé: Behav Brain Res
Pays: Netherlands
ID NLM: 8004872
Informations de publication
Date de publication:
20 04 2020
20 04 2020
Historique:
received:
24
08
2019
revised:
05
02
2020
accepted:
10
02
2020
pubmed:
15
2
2020
medline:
21
5
2021
entrez:
15
2
2020
Statut:
ppublish
Résumé
Intracerebroventricular (icv) administration of streptozotocin (STZ) has been used as a metabolic model of sporadic Alzheimer's disease (AD). Erythropoietin (EPO) possesses neuroprotective and memory-improving effects, which might be advantageous in treating different characteristics of AD. Nevertheless, the hematopoietic effect of EPO has hindered its application as a neuroprotective agent. Previous studies have shown that a new Epo derivative called carbamylated Erythropoietin-Fc (CEPO-Fc), yield noticeable neuroprotective effects without affecting hematopoiesis. In this study, the neuroprotective effects of CEPO-Fc on icv-STZ induced memory impairment and hippocampal apoptosis were examined. Adult male Wistar rats weighing 250-300 g were used. STZ was administered on days 1 and 3 (3 mg/kg in divided doses/icv), and CEPO-Fc was administered at the dose of 5000 IU/ip/daily during days 4-14. The animals were trained in Morris water maze during days 15-17, and the memory retention test was performed on the 18th day. Following behavioral studies, the animals were sacrificed and their hippocampi isolated to determine the amounts of cleaved caspase-3 (the landmark of apoptosis). The results showed that CEPO-Fc treatment at the dose of 5000 IU/kg/ip was able to prevent the learning and memory deficit induced by icv-STZ. Western blot analysis revealed that STZ prompted the cleavage of caspase-3 in the hippocampus while pretreatment with CEPO-Fc significantly reduced the cleavage of this protein. Collectively, our findings suggest that CEPO-Fc could restore STZ-induced learning and memory impairment as well as apoptosis in the hippocampal region in a rat model of sporadic AD induced by icv-STZ.
Identifiants
pubmed: 32057828
pii: S0166-4328(19)31305-1
doi: 10.1016/j.bbr.2020.112554
pii:
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Immunoglobulin Fc Fragments
0
Neuroprotective Agents
0
Recombinant Fusion Proteins
0
carbamylated erythropoietin
0
Erythropoietin
11096-26-7
Streptozocin
5W494URQ81
Casp3 protein, rat
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
112554Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflict of interests.