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

^*Corresponding author for this work

School of Physical Therapy

Research output: Contribution to journal › Journal Article › peer-review

15 Scopus citations

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
State	Published - 11 04 2018

Bibliographical note

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

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

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

Abstract

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