Treadmill Exercise Improves Motor Performance by Regulating the Plasticity of Corticostriatal Functional Connection in Hemiparkinsonian Rats

Objective: Parkinson's disease(PD) is a progressive neurodegenerative disorder that is characterized by the loss of dopamine(DA) due to the degeneration of substantia nigra pars compacta dopaminergic neurons. Functional connection changes of cortical-striatum pathway is considered to be the fundamental pathological feature of motor dysfunction in PD patients. In order to explain the possible mechanism of motor improving the behavioral function of PD model rats. This study aimed to quantify the strength of functional connectivity between the motor cortex and striatum by measuring oscillation synchronization, and to investigate the mechanism underlying behavioral improvement by exercise intervention in the view of metabotropic glutamate receptors 2/3(mGluR2/3)-mediated plasticity. Methods: Thirty adult male SD rats were randomly divided into three groups: shamoperation group(Control), PD group(PD) and PD with exercise group(PD + Ex). 6-hydroxydopamine(6-OHDA) was injected into medial forebrain bundle(MFB) in the right brain of SD rat to establish the parkinsonian rat model, and apomorphine(APO)-induced rotational test combined with TH-immunoreactivity in the striatum and substantia nigra pars compacta were performed to evaluate the reliability of PD model. Exercise intervention was applied to the PD + Ex group for 4 weeks(11 m/min, 30 min/d, 5 d/w).Locomotor behavior test were carried out at the end of 0/1/2/3/4 week; the local field potentials(LFPs) in the motorcortex and striatum of freely moving parkinsonian were recorded by using vivo multichannel recording technology; the extracellular glutamate levels and mGluR2/3 protein levels were measured by using microdialysis inserted-high performance liquid chromatography(HPLC) and biochemical tests, respectively. Results: Compared with the PD group, the PD + Ex group spent significantly more time performing fast and slow movements(P<0.05), and significantly less time in resting(P<0.05), and these improvements in locomotor behavior showed time-dependent. Electrophysiological results indicated that the coherence value and phase index between motor cortical and striatal β oscillation were both significantly decreased in PD + Ex group compared with PD group(P<0.05), and this decrease is time-dependent as well. In addition, the PD + Ex rats expressed a significant decrease in extracellular glutamate levels(P<0.01) while mGluR2/3 protein was up-regulated(P<0.01) in striatum compared with Control group.Conclusions: Low locomotor level accompanied with exaggerated synchronized beta oscillation were observed in hemiparkinsonian rats. Exercise-enhanced neuroplasticity targeting corticostriatal pathway provide a possible mechanism for revealing neural substrates underlying exercise-based neurorehabilitation, and mGluR-mediated glutamatergic transmission may serve as an attractive target in this process.