Neuroprotective effect of fingolimod and pramipexole in Parkinson's disease animal model

• Autorzy: Motyl J. , Przykaza L. , Kosson P. , Boguszewski P.M. , Strosznajder J.B.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Recently sphingolipids alterations have been shown to play an important role in pathomechanism of neurodegenerative diseases. Our last study indicated suppression of gene expression and activity of sphingosine kinases (Sphk1/2)/ sphingosine-1-phosphate (S1P) synthesis in cellular model of Parkinson’s disease (PD). Moreover, the cytoprotective effect of S1P and its analog Fingolimod (P-FTY720) in this PD model was observed. The fundamental goal of current research was to determine the impact of FTY720 and dopamine D2/D3 receptors agonist – pramipexole (PPX) on death signalling and motor activity in mice PD model. METHODS: Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 40 mg/kg) was administrated ip to adult C57BL/6 mice. FTY720 (1 mg/kg) or PPX (1 mg/kg) was injected ip during 10 days. Then behavioral tests (open field, rota-rod, and pole test) were performed. Midbrain and striatum were used for further studies. The immunochemical, spectrofluorometrical, and QPCR methods were applied. RESULTS: Our results indicated significant reduction in the number of dopaminergic cells in the midbrain of MPTP treated animals. Moreover, in this PD model alterations of Sphk1/2 and Akt kinase mediated signalling were found. It was also detected that gene expression of pro-apoptotic proteins in midbrain cells was activated. FTY720 and PPX protected dopaminergic cells against death as a result of Sphks up-regulation and apoptotic signalling suppression. In behavioural examination, MPTP mice exhibited impaired motor coordination in rota-rod test. Total time spent on the accelerating rota-rod was increased two-fold after FTY720 and PPX administration. We have also observed total distance elongation in animals treated with both above mentioned compounds during open-field test. CONCLUSIONS: In conclusion, this study indicated that FTY720 and PPX contribute to improvement of mice motor activity and they offer opportunities for PD therapy. Supported by NCN grant 2013/09/N/NZ4/02045.

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

Twórcy

autor

Motyl J.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Przykaza L.

• Laboratory of Experimental Neurosurgery, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Kosson P.

• Laboratory for Genetically Modified Animals, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Boguszewski P.M.

• Laboratory of Limbic System, Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Strosznajder J.B.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland