Synergistic Effects Of L-dopa And Treadmill Exercise In A Mouse Model Of Parkinson’s Disease

PURPOSE: Parkinson’s disease (PD) commonly occurs in people over 65. PD affects neurons and neural networks in the basal ganglia, and dopamine-producing neurons are lost in Substantia nigra pars compacta (SNpc), resulting in a dopamine deficiency in the striatum and motor dysfunction. Although administration of L-3,4-dihydroxyphenylalanine (L-dopa), which is the most representative medicine of PD, can alleviate symptoms of PD, long-term administration of L-dopa is known to cause various side effects such as dyskinesia, half-life that shortens the effectiveness of a drug, and abnormal involuntary movement. World Health Organization published that regular exercise could reduce the risk of dementia. Exercise raises various neurotrophic factors in the brain and plays a crucial role in promoting neuroprotection of neurogenesis and dopamine pathways. Therefore, the present study compared the effects of L-dopa and treadmill exercise on the PD animal model and investigated the synergistic effects of L-dopa and treadmill exercise. METHODS: Seven-week male C57BL/6 J mice were randomly separated into five groups: control group (Con, n = 12), MPTP group (MPTP, n = 12), MPTP_Exercise/L-dopa group (ME/ML, n = 12), MPTP_Exericse_L-dopa group (MEL, n = 12). MPTP was injected twice a week, every 3.5 days, for 5 weeks to induce PD. Exercise training was performed for 60 minutes a day, 5 days a week, and 8 weeks at 10 m/min (3-week), 12 m/min (3-week), and 15 m/min (2-week). L-dopa was injected for the last three weeks of exercise. RESULTS: Our study showed that ME, ML, and MEL improved motor function through behavior tests (e.g., Nest building and Rotarod), and MEL more alleviated pathological characteristics of PD than ME and ML compared to MPTP (e.g., TH and α-synuclein). Further, MEL alleviated cell proliferation factor and apoptosis activation factor more than ME and ML (e.g., ERK1/2, JNK, Bax, and Cleaved-Caspase-3). Eventually, MEL showed similar apoptosis compared to Con in the TUNEL assay. CONCLUSIONS: Our study suggests that exercise effects on PD are similar to L-dopa effects on PD, but when exercise and L-dopa were treated at the same time, synergistic effects can more alleviate motor function, cell proliferation, and apoptosis of PD compared to single treatment of exercise and L-dopa.