1. Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats
- Author
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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, and Yung-Hsiao Chiang
- Subjects
glucose-dependent insulinotropic polypeptide ,6-hydroxydopamine ,Parkinson’s disease ,neuroprotection ,incretin ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - 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.
- Published
- 2018
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