Characterization of Motor Neuron Prostaglandin E2 EP3 Receptor Isoform in a Mouse Model of Amyotrophic Lateral Sclerosis
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- Kosuge Yasuhiro
- Laboratory of Pharmacology, School of Pharmacy, Nihon University Department of Pharmacology, Tokyo Dental College
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- Miyagishi Hiroko
- Laboratory of Pharmacology, School of Pharmacy, Nihon University Department of Pharmacology, School of Pharmacy, International University of Health and Welfare
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- Shinomiya Takashi
- Department of Pharmacology, Tokyo Dental College
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- Nishiyama Kenta
- Laboratory of Pharmacology, School of Pharmacy, Nihon University
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- Suzuki Satomi
- Laboratory of Pharmacology, School of Pharmacy, Nihon University
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- Osada Nobuhiro
- Laboratory of Pharmacology, School of Pharmacy, Nihon University
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- Ishige Kumiko
- Laboratory of Pharmacology, School of Pharmacy, Nihon University
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- Okubo Migiwa
- Department of Pharmacology, Tokyo Dental College
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- Kawaguchi Mitsuru
- Department of Pharmacology, Tokyo Dental College
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- Ito Yoshihisa
- Laboratory of Pharmacology, School of Pharmacy, Nihon University
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Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with adult onset, characterized by progressive loss of motor neurons. Prostaglandin E2 (PGE2), a lipid mediator, exerts its biological functions by binding to four subtypes of E-prostanoid (EP1–4). Among them, EP3 has been shown to have multiple isoforms, EP3α, EP3β, and EP3γ, produced by alternative splicing. Since PGE2 has been shown to have important pathophysiological roles in ALS, experiments were performed to identify EP3 receptor isoform(s) in spinal motor neurons of wild-type (WT) and ALS model (G93A) mice. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of adult mice demonstrated expression of EP3α and EP3γ mRNAs in the lumbar spinal cord, whereas EP3β mRNA was barely detectable. Laser capture microdissection was used to dissect out motor neurons from frozen samples of lumbar spinal cord in these mice for analysis by real-time PCR. We found that expression of EP3γ mRNA was predominant in these neurons, whereas EP3α and EP3β mRNAs were undetectable. At the early symptomatic stage, the mRNA expression profiles of these splice isoforms in G93A motor neurons were comparable to those in neurons from WT mice. These results suggest that the PGE2-to-EP3 signaling pathway is mediated mainly by the EP3γ isoform in the motor neurons of mice, and that modulation of the EP3γ isoform in motor neurons may be a promising new therapeutic approach for ALS.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 38 (12), 1964-1968, 2015
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204634099840
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- NII論文ID
- 130005112645
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 026950597
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- PubMed
- 26632188
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- PubMed
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- 抄録ライセンスフラグ
- 使用不可