Glucose-dependent insulinotropic polypeptide mitigates 6-OHDA-induced behavioral impairments in Parkinsonian rats

Yu Wen Yu; Shih Chang Hsueh; Jing Huei Lai; Yen Hua Chen; Shuo Jhen Kang; Kai Yun Chen; Tsung Hsun Hsieh; Barry J. Hoffer; Yazhou Li; Nigel H. Greig; Yung Hsiao Chiang

doi:10.3390/ijms19041153

Glucose-dependent insulinotropic polypeptide mitigates 6-OHDA-induced behavioral impairments in Parkinsonian rats

Yu Wen Yu, Shih Chang Hsueh, Jing Huei Lai, Yen Hua Chen, Shuo Jhen Kang, Kai Yun Chen, Tsung Hsun Hsieh, Barry J. Hoffer, Yazhou Li, Nigel H. Greig, Yung Hsiao Chiang

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11 Citations (Scopus)

Abstract

In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development.

Original language	English
Article number	1153
Journal	International Journal of Molecular Sciences
Volume	19
Issue number	4
DOIs	https://doi.org/10.3390/ijms19041153
Publication status	Published - Apr 11 2018

Keywords

6-hydroxydopamine
Glucose-dependent insulinotropic polypeptide
Incretin
Neuroprotection
Parkinson’s disease

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.3390/ijms19041153

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title = "Glucose-dependent insulinotropic polypeptide mitigates 6-OHDA-induced behavioral impairments in Parkinsonian rats",

abstract = "In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development.",

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AU - Yu, Yu Wen

AU - Hsueh, Shih Chang

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AU - Chen, Yen Hua

AU - Kang, Shuo Jhen

AU - Chen, Kai Yun

AU - Hsieh, Tsung Hsun

AU - Hoffer, Barry J.

AU - Li, Yazhou

AU - Greig, Nigel H.

AU - Chiang, Yung Hsiao

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Glucose-dependent insulinotropic polypeptide mitigates 6-OHDA-induced behavioral impairments in Parkinsonian rats

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