Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats.
Yu-Wen YuShih-Chang HsuehJing-Huei LaiYen-Hua ChenShuo-Jhen KangTsung-Hsun HsiehTsung-Hsun HsiehBarry J HofferYazhou LiNigel H GreigYung-Hsiao ChiangPublished in: International journal of molecular sciences (2018)
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.
Keyphrases
- high glucose
- endothelial cells
- spinal cord injury
- systematic review
- randomized controlled trial
- minimally invasive
- blood glucose
- metabolic syndrome
- drug induced
- blood pressure
- uric acid
- combination therapy
- adipose tissue
- oxidative stress
- brain injury
- ultrasound guided
- sleep quality
- depressive symptoms
- induced pluripotent stem cells