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Int. J. Mol. Sci. 2018, 19(4), 1153; https://doi.org/10.3390/ijms19041153

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.
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)
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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. 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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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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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