Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

Prostaglandin E2 (PGE2) is a key molecule involved in the neuroinflammatory processes that characterize amyotrophic lateral sclerosis (ALS). Although PGE2 synthesis is regulated by PGE2 synthases (PGESs), the pathological role of PGESs in ALS still remains unknown. Experiments were performed to eluc...

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Main Authors: Hiroko Miyagishi, Yasuhiro Kosuge, Kumiko Ishige, Yoshihisa Ito
Format: Article
Language:English
Published: Elsevier 2012-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319305821
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author Hiroko Miyagishi
Yasuhiro Kosuge
Kumiko Ishige
Yoshihisa Ito
author_facet Hiroko Miyagishi
Yasuhiro Kosuge
Kumiko Ishige
Yoshihisa Ito
author_sort Hiroko Miyagishi
collection DOAJ
description Prostaglandin E2 (PGE2) is a key molecule involved in the neuroinflammatory processes that characterize amyotrophic lateral sclerosis (ALS). Although PGE2 synthesis is regulated by PGE2 synthases (PGESs), the pathological role of PGESs in ALS still remains unknown. Experiments were performed to elucidate the expression of PGESs and the localization of microsomal PGES-1 (mPGES-1) in neurons and glial cells in the spinal cord of ALS model (G93A) mice. Neurological symptom was observed in G93A mice from 14 weeks by the tail suspension test, and rotarod performances were decreased at 16 weeks and older. Western blotting revealed that the level of mPGES-1 was increased in G93A mice at 15 weeks and older. In contrast, the levels of cytosolic PGES and mPGES-2 did not change at any age. Immunohistochemical analysis demonstrated that age-dependent expression of mPGES-1 was found in motor neurons in G93A mice at 11 and 15 weeks. Immunoreactivity of mPGES-1 was also co-localized in Iba1-positive microglia in G93A mice at 15 weeks. These results suggest that mPGES-1 in motor neurons may play a role in the pathogenesis of ALS and that mPGES-1 may work sequentially in motor neurons and activated microglia to produce ALS symptoms in G93A mice. Keywords:: amyotrophic lateral sclerosis, motor neuron, microglia, prostaglandin E2, microsomal prostaglandin E synthase-1
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spelling doaj.art-2ff9e93bd0714ef2a2f0a481e8badb2d2022-12-21T23:42:43ZengElsevierJournal of Pharmacological Sciences1347-86132012-01-011182225236Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral SclerosisHiroko Miyagishi0Yasuhiro Kosuge1Kumiko Ishige2Yoshihisa Ito3Laboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, JapanLaboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, JapanLaboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, JapanLaboratory of Pharmacology, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan; Corresponding author. ito.yoshihisa@nihon-u.ac.jp on February 3, 2012 (in advance)Prostaglandin E2 (PGE2) is a key molecule involved in the neuroinflammatory processes that characterize amyotrophic lateral sclerosis (ALS). Although PGE2 synthesis is regulated by PGE2 synthases (PGESs), the pathological role of PGESs in ALS still remains unknown. Experiments were performed to elucidate the expression of PGESs and the localization of microsomal PGES-1 (mPGES-1) in neurons and glial cells in the spinal cord of ALS model (G93A) mice. Neurological symptom was observed in G93A mice from 14 weeks by the tail suspension test, and rotarod performances were decreased at 16 weeks and older. Western blotting revealed that the level of mPGES-1 was increased in G93A mice at 15 weeks and older. In contrast, the levels of cytosolic PGES and mPGES-2 did not change at any age. Immunohistochemical analysis demonstrated that age-dependent expression of mPGES-1 was found in motor neurons in G93A mice at 11 and 15 weeks. Immunoreactivity of mPGES-1 was also co-localized in Iba1-positive microglia in G93A mice at 15 weeks. These results suggest that mPGES-1 in motor neurons may play a role in the pathogenesis of ALS and that mPGES-1 may work sequentially in motor neurons and activated microglia to produce ALS symptoms in G93A mice. Keywords:: amyotrophic lateral sclerosis, motor neuron, microglia, prostaglandin E2, microsomal prostaglandin E synthase-1http://www.sciencedirect.com/science/article/pii/S1347861319305821
spellingShingle Hiroko Miyagishi
Yasuhiro Kosuge
Kumiko Ishige
Yoshihisa Ito
Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
Journal of Pharmacological Sciences
title Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
title_full Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
title_fullStr Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
title_full_unstemmed Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
title_short Expression of Microsomal Prostaglandin E Synthase-1 in the Spinal Cord in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis
title_sort expression of microsomal prostaglandin e synthase 1 in the spinal cord in a transgenic mouse model of amyotrophic lateral sclerosis
url http://www.sciencedirect.com/science/article/pii/S1347861319305821
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