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

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.

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

Fingerprint

Oxidopamine
Polypeptides
polypeptides
impairment
glucose
rats
Glucose
Rats
Peptides
pretreatment
anxiety
Medial Forebrain Bundle
dosage
dopamine
Pharmacokinetics
Apomorphine
field tests
abnormalities
Neuroprotective Agents
Switzerland

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

Cite this

Glucose-dependent insulinotropic polypeptide mitigates 6-OHDA-induced behavioral impairments in Parkinsonian rats. / Yu, Yu Wen; Hsueh, Shih Chang; Lai, Jing Huei; Chen, Yen Hua; Kang, Shuo Jhen; Chen, Kai Yun; Hsieh, Tsung Hsun; Hoffer, Barry J.; Li, Yazhou; Greig, Nigel H.; Chiang, Yung Hsiao.

In: International Journal of Molecular Sciences, Vol. 19, No. 4, 1153, 11.04.2018.

Research output: Contribution to journalArticle

Yu, Yu Wen ; Hsueh, Shih Chang ; Lai, Jing Huei ; Chen, Yen Hua ; Kang, Shuo Jhen ; Chen, Kai Yun ; Hsieh, Tsung Hsun ; Hoffer, Barry J. ; Li, Yazhou ; Greig, Nigel H. ; Chiang, Yung Hsiao. / Glucose-dependent insulinotropic polypeptide mitigates 6-OHDA-induced behavioral impairments in Parkinsonian rats. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 4.
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