Recruitment of the prefrontal cortex and cerebellum in Parkinsonian rats following skilled aerobic exercise.
Exercise modality and complexity play a key role in determining neurorehabilitative outcome in Parkinson's disease (PD). Exercise training (ET) that incorporates both motor skill training and aerobic exercise has been proposed to synergistically improve cognitive and automatic components of motor control in PD patients. Here we introduced such a skilled aerobic ET paradigm in a rat model of dopaminergic deafferentation. Rats with bilateral, intra-striatal 6-hydroxydopamine lesions were exposed to forced ET for 4weeks, either on a simple running wheel (non-skilled aerobic exercise, NSAE) or on a complex wheel with irregularly spaced rungs (skilled aerobic exercise, SAE). Cerebral perfusion was mapped during horizontal treadmill walking or at rest using [(14)C]-iodoantipyrine 1week after the completion of ET. Regional cerebral blood flow (rCBF) was quantified by autoradiography and analyzed in 3-dimensionally reconstructed brains by statistical parametric mapping. SAE compared to NSAE resulted in equal or greater recovery in motor deficits, as well as greater increases in rCBF during walking in the prelimbic area of the prefrontal cortex, broad areas of the somatosensory cortex, and the cerebellum. NSAE compared to SAE animals showed greater activation in the dorsal caudate-putamen and dorsal hippocampus. Seed correlation analysis revealed enhanced functional connectivity in SAE compared to NSAE animals between the prelimbic cortex and motor areas, as well as altered functional connectivity between midline cerebellum and sensorimotor regions. Our study provides the first evidence for functional brain reorganization following skilled aerobic exercise in Parkinsonian rats, and suggests that SAE compared to NSAE results in enhancement of prefrontal cortex- and cerebellum-mediated control of motor function.
Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, USA.
Zhuo
Z
Wang
Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, USA.
Yumei
Y
Guo
Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, USA.
Kalisa G
KG
Myers
Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, USA.
Ryan
R
Heintz
Department of Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, USA; Departments of Biomedical Engineering, Neurology, Cell and Neurobiology, University of Southern California, Los Angeles, CA, USA. Electronic address: holschne@usc.edu.
Daniel P
DP
Holschneider
D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001931:Brain Mapping; D002531:Cerebellum / Q000098:blood supply / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D009043:Motor Activity / Q000502:physiology; D009048:Motor Skills / Q000502:physiology*; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology* / Q000534:rehabilitation*; D010805:Physical Conditioning, Animal / Q000379:methods*; D017397:Prefrontal Cortex / Q000098:blood supply / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
Cerebellum; Exercise; Functional brain mapping; Functional connectivity; Motor adaptation; Motor function; Motor skill learning; Parkinson's disease; Prefrontal cortex; Rats; Rehabilitation