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­­Exercise protects synaptic density in a rat model of Parkinson’s disease

Lookup NU author(s): Professor David BrooksORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Background: Parkinson's disease (PD) is characterized by Lewy body and neurite pathology associated with dopamine terminal dysfunction. Clinically, it is associated with motor slowing, rigidity, and tremor. Postural instability and pain are also features.. Physical exercise benefits PD patients - possibly by promoting neuroplasticity including synaptic regeneration. Objectives: In a parkinsonian rat model, we test the hypotheses that exercise: (a) increases synaptic density and reduces neuroinflammation and (b) lowers the nociceptive threshold by increasing m-opioid receptor expression. Methods: Brain autoradiography was performed on rats unilaterally injected with either 6-hydroxydopamine (6-OHDA) or saline and subjected to treadmill exercise over 5 weeks. [3H]UCB-J was used to measure synaptic vesicle glycoprotein 2A (SV2A) density. Dopamine D2/3 receptor and m-opioid receptor availability were assessed with [3H]Raclopride and [3H]DAMGO, respectively, while neuroinflammation was detected with the 18kDA translocator protein (TSPO) marker [3H]PK11195. The nociceptive threshold was determined prior to and throughout the exercise protocol. Results: Autoradiography confirmed a dopaminegic deficit with increased striatal [3H]Raclopride D2/3 receptor availability and reduced nigral tyrosine hydroxylase immunoreactivity in the ipsilateral hemisphere of all 6-OHDA-injected rats. Sedentary rats lesioned with 6-OHDA showedsignificant reduction of ipsilateral striatal [3H]UCB-J binding and substantia nigra while [3H]PK11195 showed increased striatal neuroinflammation.. Lesioned rats who exercised had higher levels of ipsilateral striatal [3H]UCB-J binding and lower levels of neuroinflammation compared to sedentary lesioned rats. Striatal 6-OHDA injections reduced thalamic m-opioid receptor availability in the lesioned rats but this remained normal in exercised rats and raised thalamic and hippocampal SV2A synaptic density was also seen accompanied by a rise in nociceptive threshold. Conclusion: These data suggest that treadmill exercise protect nigral and striatal synaptic integrity in a rat lesion model of PD - possibly by promoting compensatory mechanisms. Exercise was also associated with reduced neuroinflammation post lesioning and altered opioid transmission resulting in an increased nociceptive threshold.

Publication metadata

Author(s): Binda KH, Lillethorup TP, Real CC, Bærentzen SL, Nielsen MN, Orlowski D, Brooks DJ, Chacur M, Landau AM

Publication type: Article

Publication status: Published

Journal: Experimental Neurology

Year: 2021

Volume: 342

Online publication date: 11/05/2021

Acceptance date: 04/05/2021

Date deposited: 04/05/2021

ISSN (electronic): 0014-4886

Publisher: Elsevier


DOI: 10.1016/j.expneurol.2021.113741


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