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Open AccessArticle

Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats

1
The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
2
Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei 11031, Taiwan
3
Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
4
Department of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
5
Department of Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
6
Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 20892, USA
7
Department of Neurosurgery, Taipei Medical University Hospital, Taipei 11031, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(4), 1153; https://doi.org/10.3390/ijms19041153
Received: 12 March 2018 / Revised: 4 April 2018 / Accepted: 6 April 2018 / Published: 11 April 2018
(This article belongs to the Special Issue Molecular Research on Neurodegenerative Diseases)
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. View Full-Text
Keywords: glucose-dependent insulinotropic polypeptide; 6-hydroxydopamine; Parkinson’s disease; neuroprotection; incretin glucose-dependent insulinotropic polypeptide; 6-hydroxydopamine; Parkinson’s disease; neuroprotection; incretin
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Yu, Y.-W.; Hsueh, S.-C.; Lai, J.-H.; Chen, Y.-H.; Kang, S.-J.; Chen, K.-Y.; Hsieh, T.-H.; Hoffer, B.J.; Li, Y.; Greig, N.H.; Chiang, Y.-H. Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats. Int. J. Mol. Sci. 2018, 19, 1153.

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