The influence of phosphodiesterase inhibitors on degradation and neuroinflammation in the mouse model of Parkinson's disease

• Autorzy: Schwenkgrub J. , Zaremba M. , Joniec-Maciejak I. , Cudna A. , Mirowska-Guzel D. , Kurkowska-Jastrzebska I.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: A neuroprotective or disease modifying treatment of Parkinson’s disease (PD) still remains an unmet need. The non-clinical and clinical studies have indicated that cyclic nucleotide phosphodiesterase (PDE) inhibitors represent a novel class of drugs which may be useful in treating neuroinflammation disorders. The present study was designed to examine the efficacy of PDE inhibitors, ibudilast (IBD) and vinpocetine (VPC) in the mice model of PD induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). METHODS: 3 months-old male C57Bl/10Tar mice were treated with IBD (0, 20, 30, 40 or 50 mg/kg) BID for 9 days or VPC (0, 10, 20 or 30 mg/kg) once daily for 8 consecutive days (beginning 2 days or 1 day prior to MPTP (60 mg/kg) intoxication, respectively). Rotarod test was conducted on day 3 post MPTP injection. Mice were sacrificed 7 days after MPTP intoxication. IL-1β, IL-6, TNF-α and GDNF mRNA expression in the striatum was examined by the Real Time RT-PCR method. Western blot analysis was used to estimate tyrosine hydroxylase (TH) expression, micro- and astroglia activation markers (Iba1 and GFAP, respectively). Dopamine (DA) metabolism was evaluated by HPLC method. RESULTS: Chronic administration of PDE inhibitors attenuated astroglial reactivity and increased glial cell-derived neurotrophic factor (GDNF) gene expression in the striatum. IBD reduced TNF-α, IL-6 and IL-1β expressions, whereas VPC had no impact on elevated levels of TNF-α. Moreover,  mice receiving 40 mg/ kg IBD showed significant improvement in the locomotor activity compared to control. However, PDE inhibitors did not change DA metabolism and TH expression in the striatum. CONCLUSIONS: The findings provide evidence for the glia-derived protective properties of PDE inhibitors in the MPTP-induced model of PD. This response may be promising for the better outcome in the later stages of neurodegeneration. However, the further study is needed to confirm such possibility.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S61-S62

Twórcy

autor

Schwenkgrub J.

• Centre for Preclinical Research and Technology, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Zaremba M.

• Centre for Preclinical Research and Technology, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Joniec-Maciejak I.

• Centre for Preclinical Research and Technology, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Cudna A.

• Centre for Preclinical Research and Technology, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Mirowska-Guzel D.

• Centre for Preclinical Research and Technology, Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland

autor

Kurkowska-Jastrzebska I.

• 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland