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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish
Article number1153
JournalInternational Journal of Molecular Sciences
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 11 2018

Keywords

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

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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