Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats

Akihiko Kondo; Tetsuro Shingo; Takao Yasuhara; Satoshi Kuramoto; Masahiro Kameda; Yoichiro Kikuchi; Toshihiro Matsui; Yasuyuki Miyoshi; Takashi Agari; Cesario V. Borlongan; Isao Date

doi:10.1016/j.brainres.2009.08.025

Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats

Akihiko Kondo, Tetsuro Shingo, Takao Yasuhara, Satoshi Kuramoto, Masahiro Kameda, Yoichiro Kikuchi, Toshihiro Matsui, Yasuyuki Miyoshi, Takashi Agari, Cesario V. Borlongan, Isao Date

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23 Citations (Scopus)

Abstract

We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1 mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1 mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6 h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.

Original language	English
Pages (from-to)	127-136
Number of pages	10
Journal	Brain Research
Volume	1296
DOIs	https://doi.org/10.1016/j.brainres.2009.08.025
Publication status	Published - Oct 16 2009

Keywords

Apoptosis
Cell proliferation
Generalized seizure
Neuropeptide Y
Neuroprotection

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/j.brainres.2009.08.025

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Kondo, A., Shingo, T., Yasuhara, T., Kuramoto, S., Kameda, M., Kikuchi, Y., Matsui, T., Miyoshi, Y., Agari, T., Borlongan, C. V., & Date, I. (2009). Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats. Brain Research, 1296, 127-136. https://doi.org/10.1016/j.brainres.2009.08.025

Kondo, A, Shingo, T, Yasuhara, T, Kuramoto, S, Kameda, M, Kikuchi, Y, Matsui, T, Miyoshi, Y, Agari, T, Borlongan, CV & Date, I 2009, 'Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats', Brain Research, vol. 1296, pp. 127-136. https://doi.org/10.1016/j.brainres.2009.08.025

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title = "Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats",

abstract = "We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1 mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1 mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6 h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.",

keywords = "Apoptosis, Cell proliferation, Generalized seizure, Neuropeptide Y, Neuroprotection",

author = "Akihiko Kondo and Tetsuro Shingo and Takao Yasuhara and Satoshi Kuramoto and Masahiro Kameda and Yoichiro Kikuchi and Toshihiro Matsui and Yasuyuki Miyoshi and Takashi Agari and Borlongan, {Cesario V.} and Isao Date",

note = "Funding Information: This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan ; and by a Research grant from the Japan Epilepsy Research Foundation .",

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doi = "10.1016/j.brainres.2009.08.025",

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AU - Kondo, Akihiko

AU - Shingo, Tetsuro

AU - Yasuhara, Takao

AU - Kuramoto, Satoshi

AU - Kameda, Masahiro

AU - Kikuchi, Yoichiro

AU - Matsui, Toshihiro

AU - Miyoshi, Yasuyuki

AU - Agari, Takashi

AU - Borlongan, Cesario V.

AU - Date, Isao

N1 - Funding Information: This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan ; and by a Research grant from the Japan Epilepsy Research Foundation .

PY - 2009/10/16

Y1 - 2009/10/16

N2 - We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1 mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1 mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6 h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.

AB - We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1 mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1 mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6 h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.

KW - Apoptosis

KW - Cell proliferation

KW - Generalized seizure

KW - Neuropeptide Y

KW - Neuroprotection

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Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats

Abstract

Keywords

ASJC Scopus subject areas

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