Deneysel Parkinson Hastalığı Modelinde Mitokondri Transplantasyonu ve Egzersizin Etkilerinin Karşılaştırılması

Abstract

Parkinson's disease (PD) is associated with degeneration of dopamine-secreting neurons in the brain. PD manifests itself with impaired locomotor and spontaneous activities, such as difficulty initiating movement, tremors, and making slow and small movements, and PD develops slowly over years. Mitochondrial dysfunction in dopaminergic neurons is among the many different causes of PD. Recently, exogenous mitochondrial transplantation has been reported to help treat mitochondrial dysfunction and alleviate the clinical symptoms of PD. The beneficial effect of exercise is documented clearly in PD. The aim of the study was to investigate the therapeutic effects of exercise and mitochondrial transplantation in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. MPTP was injected intraperitoneally into C57BL mice. The injections were administered on the same day with a dose of 20 mg/kg, 4 times, 2 h apart. After 7 days of the development of PD, treadmill exercises were done for 30 minutes, 5 days a week, at a speed of 20 m/min for 4 weeks. Healthy mitochondria isolated from mouse liver were transplanted into the brain of the treatment groups intranasally, four times with a one-week interval. Spontaneous activity and locomotor activity tests were applied to all groups in three different sessions (before PD, after PD, and at the end of treatment). Movement of intranasally transplanted mitochondria to the brain was observed with fluorescence microscopy. In the exercise groups and the groups receiving mitochondrial treatment, PD symptoms decreased in terms of activity tests. In addition, molecular studies in brain showed that the Bax/Bcl-2 ratio decreased in the exercise groups, but this decrease was reversed in the mitochondrial groups. Contrary to expectations, mitochondrial transplantation had negative effects in molecular terms. It was concluded that it caused an increase in Caspase 1 and 3 proteins and therefore could trigger apoptotic processes in the brain. It has been determined that the synergistic effects mitochondria and exercise seen in behavioral tests do not occur at the molecular level. Exercise is a traditional approach that reduces symptoms in PD. Moreover, intranasal delivery of mitochondria to the brain is a promising treatment method as it is non-invasive and easily applicable to humans. However, the results obtained show that delivering very large structures such as mitochondria in this way is not very effective. In addition, it has left question marks on the use of mitochondria in neurodegenerative diseases.