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.
ASJC Scopus subject areas
- Molecular Biology
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
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. (2018). Glucose-dependent insulinotropic polypeptide mitigates 6-OHDA-induced behavioral impairments in Parkinsonian rats. International Journal of Molecular Sciences, 19(4), . https://doi.org/10.3390/ijms19041153