Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model

The purpose of this study was to determine the effectiveness of the systemic administration of high dose erythropoietin (EPO) in a 6-hydroxydopamine (6-OHDA)- induced rat model. Rats were divided into 7 groups. Groups 1–4 were administered daily EPO doses of 0; 2,500; 5,000 and 10,000 U/kg via intra...

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Main Authors:	QI, CHEN, XU, MINGXIN, GAN, JING, YANG, XINXIN, WU, NA, SONG, LU, YUAN, WEIEN, LIU, ZHENGUO
Format:	Online
Language:	English
Published:	D.A. Spandidos 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094589/

id	pubmed-4094589
recordtype	oai_dc
spelling	pubmed-40945892014-07-14 Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model QI, CHEN XU, MINGXIN GAN, JING YANG, XINXIN WU, NA SONG, LU YUAN, WEIEN LIU, ZHENGUO Articles The purpose of this study was to determine the effectiveness of the systemic administration of high dose erythropoietin (EPO) in a 6-hydroxydopamine (6-OHDA)- induced rat model. Rats were divided into 7 groups. Groups 1–4 were administered daily EPO doses of 0; 2,500; 5,000 and 10,000 U/kg via intraperitoneal injection (i.p.) for 5 days. The EPO concentration in cerebrospinal fluid (CSF) was determined by enzyme-linked immunosorbent assay (ELISA) and western blot analysis. The dose of 10,000 U/kg was then selected for subsequent experiments. In group 5, rats received saline via medial forebrain bundle (MFB). In group 6, rats received 6-OHDA via MFB. In group 7, an EPO concentration of 10,000 U/kg was constantly administered i.p. for 5 days to rats prior to 6-OHDA injection via MFB. Behavioral analysis was performed for groups 5–7 by rat rotation tests. The number of tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN) was measured by immunocytochemistry. The activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinases (MAPKs) and caspase-3 signaling in rats were analyzed using western blotting. The results showed that there was a significant increase in EPO levels in the CSF in 10,000 U/kg group compared with the 2,500 and 5,000 U/kg groups (P<0.01). Significantly fewer rotational counts were obtained in rats that were pretreated with EPO compared with saline-pretreated 6-OHDA-lesioned rats (P<0.001). The dopaminergic neurons in the 6-OHDA-lesioned SN were also increased in the EPO-pretreated rats when compared with control rats (P<0.01). Western blot analysis revealed that EPO inhibited the 6-OHDA-induced activation of JNK, ERK, p38 MAPK and caspase-3 signaling in the rat model. In conclusion, systemic administration of a high dose of EPO exerted neuroprotective effects in reversing behavioral deficits associated with Parkinson’s disease and prevented loss of the dopaminergic neurons through the MAPK pathway. D.A. Spandidos 2014-08 2014-06-17 /pmc/articles/PMC4094589/ /pubmed/24939444 http://dx.doi.org/10.3892/ijmm.2014.1810 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	QI, CHEN XU, MINGXIN GAN, JING YANG, XINXIN WU, NA SONG, LU YUAN, WEIEN LIU, ZHENGUO
spellingShingle	QI, CHEN XU, MINGXIN GAN, JING YANG, XINXIN WU, NA SONG, LU YUAN, WEIEN LIU, ZHENGUO Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model
author_facet	QI, CHEN XU, MINGXIN GAN, JING YANG, XINXIN WU, NA SONG, LU YUAN, WEIEN LIU, ZHENGUO
author_sort	QI, CHEN
title	Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model
title_short	Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model
title_full	Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model
title_fullStr	Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model
title_full_unstemmed	Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model
title_sort	erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model
description	The purpose of this study was to determine the effectiveness of the systemic administration of high dose erythropoietin (EPO) in a 6-hydroxydopamine (6-OHDA)- induced rat model. Rats were divided into 7 groups. Groups 1–4 were administered daily EPO doses of 0; 2,500; 5,000 and 10,000 U/kg via intraperitoneal injection (i.p.) for 5 days. The EPO concentration in cerebrospinal fluid (CSF) was determined by enzyme-linked immunosorbent assay (ELISA) and western blot analysis. The dose of 10,000 U/kg was then selected for subsequent experiments. In group 5, rats received saline via medial forebrain bundle (MFB). In group 6, rats received 6-OHDA via MFB. In group 7, an EPO concentration of 10,000 U/kg was constantly administered i.p. for 5 days to rats prior to 6-OHDA injection via MFB. Behavioral analysis was performed for groups 5–7 by rat rotation tests. The number of tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN) was measured by immunocytochemistry. The activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinases (MAPKs) and caspase-3 signaling in rats were analyzed using western blotting. The results showed that there was a significant increase in EPO levels in the CSF in 10,000 U/kg group compared with the 2,500 and 5,000 U/kg groups (P<0.01). Significantly fewer rotational counts were obtained in rats that were pretreated with EPO compared with saline-pretreated 6-OHDA-lesioned rats (P<0.001). The dopaminergic neurons in the 6-OHDA-lesioned SN were also increased in the EPO-pretreated rats when compared with control rats (P<0.01). Western blot analysis revealed that EPO inhibited the 6-OHDA-induced activation of JNK, ERK, p38 MAPK and caspase-3 signaling in the rat model. In conclusion, systemic administration of a high dose of EPO exerted neuroprotective effects in reversing behavioral deficits associated with Parkinson’s disease and prevented loss of the dopaminergic neurons through the MAPK pathway.
publisher	D.A. Spandidos
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094589/
_version_	1613112576379453440

Erythropoietin improves neurobehavior by reducing dopaminergic neuron loss in a 6-hydroxydopamine-induced rat model

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