Erythropoietin Induction by Electroconvulsive Seizure, Gene Regulation, and Antidepressant-Like Behavioral Effects

Matthew J. Girgenti, Joshua Hunsberger, Catharine H. Duman, Monica Sathyanesan, Rose Terwilliger, Samuel S. Newton

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Background: The neuroprotective and trophic actions of erythropoietin (EPO) have been tested in several animal models of insult, injury, and neurodegeneration. Recent studies in human volunteers demonstrated that EPO improves cognition and also elicits antidepressant effects. It is believed that the behavioral effects are mediated by EPO's trophic effect on neuronal systems. We therefore tested whether EPO is able to alter behavior and brain gene expression in rats. Methods: The expression of EPO and EPO receptor (EPOR) in multiple brain regions was examined by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. The regulation of EPO and the transcription factor hypoxia-induced factor-alpha (HIF1α) after electroconvulsive seizure (ECS) was investigated. Behavioral effects of EPO were tested in the rodent forced swimming and novelty-induced hypophagia (NIH) models. EPO gene profiles were obtained by microarray analysis of the hippocampus after intracerebroventricular infusion. Results: EPO and EPOR were widely expressed in the brain albeit at low levels. Highest level of EPO and EPOR were in the choroid plexus and striatum, respectively. Peripheral administration of EPO was sufficient to produce a robust antidepressant-like effect in the forced swim and NIH tests. Gene expression profiles revealed that EPO induces the expression of neurotrophic genes such as brain-derived neurotrophic factor, VGF (nonacronymic), and neuritin. Conclusions: EPO is induced by ECS and independently exhibits antidepressant-like efficacy in the forced swim and NIH tests. EPO regulates the expression of genes implicated in antidepressant action and appears to be a candidate molecule for further testing in neuropsychiatry.

Original languageEnglish (US)
Pages (from-to)267-274
Number of pages8
JournalBiological Psychiatry
Volume66
Issue number3
DOIs
StatePublished - Aug 1 2009

Fingerprint

Erythropoietin
Antidepressive Agents
Seizures
Genes
Erythropoietin Receptors
Gene Expression
Brain
Neuropsychiatry
Intraventricular Infusions
Choroid Plexus
Brain-Derived Neurotrophic Factor
Microarray Analysis
Transcriptome
Cognition
In Situ Hybridization
Volunteers
Rodentia
Hippocampus
Transcription Factors
Animal Models

Keywords

  • Antidepressant
  • electroconvulsive seizure
  • erythropoietin
  • forced swimming test
  • gene expression
  • microarray

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Erythropoietin Induction by Electroconvulsive Seizure, Gene Regulation, and Antidepressant-Like Behavioral Effects. / Girgenti, Matthew J.; Hunsberger, Joshua; Duman, Catharine H.; Sathyanesan, Monica; Terwilliger, Rose; Newton, Samuel S.

In: Biological Psychiatry, Vol. 66, No. 3, 01.08.2009, p. 267-274.

Research output: Contribution to journalArticle

Girgenti, Matthew J. ; Hunsberger, Joshua ; Duman, Catharine H. ; Sathyanesan, Monica ; Terwilliger, Rose ; Newton, Samuel S. / Erythropoietin Induction by Electroconvulsive Seizure, Gene Regulation, and Antidepressant-Like Behavioral Effects. In: Biological Psychiatry. 2009 ; Vol. 66, No. 3. pp. 267-274.
@article{bec3e337150a4e5d8ced61803cb2a865,
title = "Erythropoietin Induction by Electroconvulsive Seizure, Gene Regulation, and Antidepressant-Like Behavioral Effects",
abstract = "Background: The neuroprotective and trophic actions of erythropoietin (EPO) have been tested in several animal models of insult, injury, and neurodegeneration. Recent studies in human volunteers demonstrated that EPO improves cognition and also elicits antidepressant effects. It is believed that the behavioral effects are mediated by EPO's trophic effect on neuronal systems. We therefore tested whether EPO is able to alter behavior and brain gene expression in rats. Methods: The expression of EPO and EPO receptor (EPOR) in multiple brain regions was examined by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. The regulation of EPO and the transcription factor hypoxia-induced factor-alpha (HIF1α) after electroconvulsive seizure (ECS) was investigated. Behavioral effects of EPO were tested in the rodent forced swimming and novelty-induced hypophagia (NIH) models. EPO gene profiles were obtained by microarray analysis of the hippocampus after intracerebroventricular infusion. Results: EPO and EPOR were widely expressed in the brain albeit at low levels. Highest level of EPO and EPOR were in the choroid plexus and striatum, respectively. Peripheral administration of EPO was sufficient to produce a robust antidepressant-like effect in the forced swim and NIH tests. Gene expression profiles revealed that EPO induces the expression of neurotrophic genes such as brain-derived neurotrophic factor, VGF (nonacronymic), and neuritin. Conclusions: EPO is induced by ECS and independently exhibits antidepressant-like efficacy in the forced swim and NIH tests. EPO regulates the expression of genes implicated in antidepressant action and appears to be a candidate molecule for further testing in neuropsychiatry.",
keywords = "Antidepressant, electroconvulsive seizure, erythropoietin, forced swimming test, gene expression, microarray",
author = "Girgenti, {Matthew J.} and Joshua Hunsberger and Duman, {Catharine H.} and Monica Sathyanesan and Rose Terwilliger and Newton, {Samuel S.}",
year = "2009",
month = "8",
day = "1",
doi = "10.1016/j.biopsych.2008.12.005",
language = "English (US)",
volume = "66",
pages = "267--274",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "3",

}

TY - JOUR

T1 - Erythropoietin Induction by Electroconvulsive Seizure, Gene Regulation, and Antidepressant-Like Behavioral Effects

AU - Girgenti, Matthew J.

AU - Hunsberger, Joshua

AU - Duman, Catharine H.

AU - Sathyanesan, Monica

AU - Terwilliger, Rose

AU - Newton, Samuel S.

PY - 2009/8/1

Y1 - 2009/8/1

N2 - Background: The neuroprotective and trophic actions of erythropoietin (EPO) have been tested in several animal models of insult, injury, and neurodegeneration. Recent studies in human volunteers demonstrated that EPO improves cognition and also elicits antidepressant effects. It is believed that the behavioral effects are mediated by EPO's trophic effect on neuronal systems. We therefore tested whether EPO is able to alter behavior and brain gene expression in rats. Methods: The expression of EPO and EPO receptor (EPOR) in multiple brain regions was examined by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. The regulation of EPO and the transcription factor hypoxia-induced factor-alpha (HIF1α) after electroconvulsive seizure (ECS) was investigated. Behavioral effects of EPO were tested in the rodent forced swimming and novelty-induced hypophagia (NIH) models. EPO gene profiles were obtained by microarray analysis of the hippocampus after intracerebroventricular infusion. Results: EPO and EPOR were widely expressed in the brain albeit at low levels. Highest level of EPO and EPOR were in the choroid plexus and striatum, respectively. Peripheral administration of EPO was sufficient to produce a robust antidepressant-like effect in the forced swim and NIH tests. Gene expression profiles revealed that EPO induces the expression of neurotrophic genes such as brain-derived neurotrophic factor, VGF (nonacronymic), and neuritin. Conclusions: EPO is induced by ECS and independently exhibits antidepressant-like efficacy in the forced swim and NIH tests. EPO regulates the expression of genes implicated in antidepressant action and appears to be a candidate molecule for further testing in neuropsychiatry.

AB - Background: The neuroprotective and trophic actions of erythropoietin (EPO) have been tested in several animal models of insult, injury, and neurodegeneration. Recent studies in human volunteers demonstrated that EPO improves cognition and also elicits antidepressant effects. It is believed that the behavioral effects are mediated by EPO's trophic effect on neuronal systems. We therefore tested whether EPO is able to alter behavior and brain gene expression in rats. Methods: The expression of EPO and EPO receptor (EPOR) in multiple brain regions was examined by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. The regulation of EPO and the transcription factor hypoxia-induced factor-alpha (HIF1α) after electroconvulsive seizure (ECS) was investigated. Behavioral effects of EPO were tested in the rodent forced swimming and novelty-induced hypophagia (NIH) models. EPO gene profiles were obtained by microarray analysis of the hippocampus after intracerebroventricular infusion. Results: EPO and EPOR were widely expressed in the brain albeit at low levels. Highest level of EPO and EPOR were in the choroid plexus and striatum, respectively. Peripheral administration of EPO was sufficient to produce a robust antidepressant-like effect in the forced swim and NIH tests. Gene expression profiles revealed that EPO induces the expression of neurotrophic genes such as brain-derived neurotrophic factor, VGF (nonacronymic), and neuritin. Conclusions: EPO is induced by ECS and independently exhibits antidepressant-like efficacy in the forced swim and NIH tests. EPO regulates the expression of genes implicated in antidepressant action and appears to be a candidate molecule for further testing in neuropsychiatry.

KW - Antidepressant

KW - electroconvulsive seizure

KW - erythropoietin

KW - forced swimming test

KW - gene expression

KW - microarray

UR - http://www.scopus.com/inward/record.url?scp=67649398867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649398867&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2008.12.005

DO - 10.1016/j.biopsych.2008.12.005

M3 - Article

C2 - 19185286

AN - SCOPUS:67649398867

VL - 66

SP - 267

EP - 274

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 3

ER -