Objective: The goal of this study is to characterize microvascular changes in the SNpc in response to a neuroprotective bout of exercise.

Background: Parkinson’s disease (PD) is a debilitating neurological disorder that affects 2% of the population aged 50 and older. Characteristic PD pathology includes loss of dopaminergic (DA) neurons in the Substantia Nigra pars compacta (SNpc). Loss of 60-70% of these neurons manifests in motor symptoms. Currently addressed with drugs/surgery, these treatments fail to slow disease progression. Epidemiological studies offer an intervention that appears to slow physical motor symptom progression, may protect DA neurons from further degeneration and lowers the risk of developing the disease:exercise. Aerobic exercise has been shown to stop progression of motor symptoms in humans, and protect against neuronal pathology in mice. The mechanisms underlying exercise-induced neuroprotection from PD symptoms remain largely unknown. Previous work in our lab has shown that administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes a 40% loss of DA neurons in the SNpc of standard-house mice, compared to a 5% loss in exercised mice. We demonstrated that one mechanism underlying this is exercise’s ability to cause cellular hypoxia in the SNpc. Cellular hypoxia induces transcription of target genes that include those to increase angiogenesis. DA neurons in the healthy SNpc have intimate spatial relationships with capillaries. In PD patients, normal contacts between DA neurons and capillaries are lost at early disease stages, accompanied by abnormal capillary morphology. Exercise has profound angiogenic capabilities in the muscular and cardiovascular systems, but exercise-induced microvascular changes have yet to be characterized in the SNpc in the context of neuroprotection.

Method: Using Vesselucida360, we can reconstruct a model of the microvasculature and characterize angiogenesis in the SNpc in response to exercise.

Results: We found an increase in proximity between DA neurons and vasculature in response to exercise and characterized the microvascular environment within the SNpc, with focus on capillary sprouting and pericyte coverage.

Conclusion: We demonstrate a positive correlation between exercise and vessel-DA neuron proximity, and changes in the microvascular environment of the SNpc.

Presented at: Society for Neuroscience, Washington, DC, November 13, 2023

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exercise-induced-angiogenesis-and-midbrain-neuroprotection-in-a-mouse-model-of-experimental-pd/