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   <subfield code="a">Running wheel activity restores MPTP-induced functional deficits</subfield>
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   <subfield code="c">[Anders Fredriksson, Ingels Stigsdotter, Anders Hurtig, Béatrice Ewalds-Kvist, Trevor Archer]</subfield>
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   <subfield code="a">Wheel-running and treadmill running physical exercise have been shown to alleviate parkinsonism in both laboratory and clinical studies. MPTP was administered to C57/BL6 mice using two different procedures: (a) administration of a double-dose regime (MPTP 2×20 or 2×40mg/kg, separated by a 24-h interval), vehicle (saline 5ml/kg) or saline (vehicle 2×5ml/kg), and (b) administration of a single-dose weekly regime (MPTP 1×40mg/kg) or saline (vehicle 1×5ml/kg) repeated over 4 consecutive weeks. For each procedure, two different physical exercise regimes were followed: (a) after the double-dose MPTP regime, mice were given daily 30-min periods of wheel-running exercise over 5 consecutive days/week or placed in a cage in close proximity to the running wheels for 3weeks. (b) Mice were either given wheel-running activity on 4 consecutive days (30-min periods) or placed in a cage nearby for 14weeks. Behavioral testing was as follows: (a) after 3weeks of exercise/no exercise, mice were tested for spontaneous motor activity (60min) and subthreshold l-Dopa (5mg/kg)-induced activity. (b) Spontaneous motor activity was measured on the fifth day during each of the each of the first 5weeks (Tests 1-5), about 1h before injections (first 4weeks), and continued on the 5th days of the 6th to the 14th weeks (Tests 6-14). Subthreshold l-Dopa (5mg/kg)-induced activity was tested on the 6th, 8th, 10th, 12th and 14th weeks. (b) Mice from the single-dose MPTP weekly regime were killed during the 15th week and striatal regions taken for dopamine analysis, whereas frontal and parietal cortex and hippocampus were taken for analysis of brain-derived neurotrophic factor (BDNF). It was shown that in both experiments, i.e., the double-dose regime and single-dose weekly regime of MPTP administration, physical activity attenuated markedly the MPTP-induced akinesia/hypokinesia in both the spontaneous motor activity and restored motor activity completely in subthreshold l-Dopa tests. Running wheel activity attenuated markedly the loss of dopamine due to repeated administrations of MPTP. BDNF protein level in the parietal cortex was elevated by the MPTP insult and increased further by physical exercise. Physical running wheel exercise alleviated both the functional and biomarker expressions of MPTP-induced parkinsonism.</subfield>
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   <subfield code="a">Exercise</subfield>
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