Amyloid β protein impairs motor function via thromboxane A2 in the rat striatum

Tatsurou Yagami; Yukio Takahara; Chiyomi Ishibashi; Gaku Sakaguchi; Naohiro Itoh; Keiichi Ueda; Hitoshi Nakazato; Noboru Okamura; Yoshiharu Hiramatsu; Tsunetoshi Honma; Akinori Arimura; Toshiyuki Sakaeda; Goro Katsuura

Neurobiology of Disease (Aug 2004)

Amyloid β protein impairs motor function via thromboxane A2 in the rat striatum

Tatsurou Yagami,
Yukio Takahara,
Chiyomi Ishibashi,
Gaku Sakaguchi,
Naohiro Itoh,
Keiichi Ueda,
Hitoshi Nakazato,
Noboru Okamura,
Yoshiharu Hiramatsu,
Tsunetoshi Honma,
Akinori Arimura,
Toshiyuki Sakaeda,
Goro Katsuura

Affiliations

Tatsurou Yagami: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Yukio Takahara: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Chiyomi Ishibashi: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Gaku Sakaguchi: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Naohiro Itoh: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Keiichi Ueda: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Hitoshi Nakazato: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Noboru Okamura: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Yoshiharu Hiramatsu: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Tsunetoshi Honma: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Akinori Arimura: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Toshiyuki Sakaeda: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan
Goro Katsuura: Discovery Research Laboratories, Shionogi and Co., Ltd., Fukushima, Osaka 553-0002, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University, School of Medicine, Yokohama, Japan; Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe, Japan

Journal volume & issue: Vol. 16, no. 3
pp. 481 – 489

Abstract

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Amyloid β protein (Aβ) deposits are found in the striatum of patients with Alzheimer disease (AD) showing extrapyramidal motor dysfunction, but neuronal cell loss has not yet been detected. To clarify how Aβ impairs motor function, we analyzed intrastriatally Aβ-injected rats. Unilateral injection of Aβ(25-35) enhanced apomorphine-induced circling in an ipsilateral direction, indicating ipsilateral dysfunction of dopaminergic nigrostriatal pathways. Volumes of lesion in the Aβ(25-35)-injected striata were significantly higher than those in the saline-injected ones. The correlation between lesion volume and circling behavior was close to significance, but slightly too low, suggesting the possible involvement of other factors in the striatal dysfunction. Aβ(25-35) significantly elevated the level of thromboxane A2 (TXA2). A stable TXA2 agonist, U46619, enhanced circling behavior, and TXA2 receptor antagonists attenuated U46619- and Aβ(25-35)-enhanced circling behavior. This study demonstrated that Aβ(25-35) impairs the motor function of dopaminergic neurons via neuronal cell loss and TXA2. It also sheds light on the therapeutic potential of TXA2 receptor blockers for the neurotoxicity of Aβ.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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