Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4346319 | Neuroscience Letters | 2010 | 6 Pages |
Abstract
Exercise preconditioning has been shown to reduce neuronal damage in ischemic/reperfusion (I/R) injury. ERK1/2 signaling in injury has been thought to modulate neuroprotection. In this study, we investigated the effects of ERK1/2 activation on the expression and activity of MMP-9 and downstream neuronal apoptosis. Adult male Sprague-Dawley rats were subjected to 30 min of exercise on a treadmill for 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Apoptotic protein caspase-3 and neuronal apoptosis in cortex and striatum was determined by Western blot at 24 h reperfusion and TUNEL staining at 48 h reperfusion in 5 I/R injury groups: no treatment, MMP-9 inhibitor (doxycycline), pre-ischemic exercise, exercised animals undergone ERK1/2 inhibition (U0126), and dual inhibition of ERK1/2 and MMP-9 in exercised ischemic rats. Cerebral MMP-9 expression in ischemic rats with different treatment was determined at 6, 12 and 24 h reperfusion by real-time PCR for mRNA, Western blot for protein and zymography for enzyme activity. Exercise preconditioning significantly (p < 0.05) reduced apoptosis determined by caspase-3 and TUNEL. In non-exercised rats, doxycycline treatment had significant (p < 0.05) reductions in apoptosis after I/R injury. The dual ERK1/2-MMP-9 inhibited exercised animals had significantly (p < 0.05) reduced neuronal apoptosis that was similar to that seen in exercised ischemic rats. MMP-9 expression in I/R injury was significantly (p < 0.05) reduced in the exercised animals as compared to non-exercised controls. When ERK1/2 was inhibited, the reduced MMP-9 expression was reversed to the level seen in the non-exercised controls. This study has suggested that exercise-induced neuroprotection in I/R injury may be mediated by MMP-9 and ERK1/2 expression, leading to a reduction in neuronal apoptosis.
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
Khawar Chaudhry, Ryan Rogers, Miao Guo, Qin Lai, Gunjan Goel, Brandon Liebelt, Xunming Ji, Alecia Curry, Aaron Carranza, David F. Jimenez, Yuchuan Ding,