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

Autor(es)

Binda, K. H. ^{[1, 2, 3]} ; Lillethorup, T. P. ^[3] ; Real, C. C. ^{[2, 3, 4]} ; Baerentzen, S. L. ^{[2, 3]} ; Nielsen, M. N. ^[2] ; Orlowski, D. ^{[5, 6]} ; Brooks, D. J. ^{[3, 7]} ; Chacur, M. ^[1] ; Landau, A. M. ^{[2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Anat, Lab Funct Neuroanat Pain, Sao Paulo, SP - Brazil

^[2] Aarhus Univ, Translat Neuropsychiat Unit, Univ Byen 13, Bldg 2b, DK-8000 Aarhus C - Denmark

^[3] Aarhus Univ & Hosp, Dept Nucl Med & PET, Palle Juul Jensens Blvd 165, J109, DK-8200 Aarhus N - Denmark

^[4] Univ Sao Paulo, Fac Med FMUSP, Lab Nucl Med LIM 43, Sao Paulo, SP - Brazil

^[5] Aarhus Univ Hosp, Ctr Expt Neurosci CENSE, Dept Clin Med, DK-8200 Aarhus N - Denmark

^[6] Aarhus Univ Hosp, Dept Neurosurg, DK-8200 Aarhus N - Denmark

^[7] Newcastle Univ, Inst Translat & Clin Res, Newcastle Upon Tyne NE4 5PL, Tyne & Wear - England

• Tipo de documento: Artigo Científico
• Fonte: Experimental Neurology; v. 342, AUG 2021.
• Citações Web of Science: 0

Resumo

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 mu-opioid receptor expression. Methods: Brain autoradiography was performed on rats unilaterally injected with either 6-hydroxydopamine (6OHDA) 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 mu-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: We 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 showed significant reduction of ipsilateral striatal and substantia nigra {[}3H]UCB-J binding while {[}3H]PK11195 showed increased ipsilateral 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 mu-opioid receptor availability but subsequent exercise restored binding. Exercise also raised thalamic and hippocampal SV2A synaptic density in 6-OHDA lesioned rats, accompanied by a rise in nociceptive threshold. Conclusion: These data suggest that treadmill exercise protects 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. (AU)

• Processo FAPESP: 17/26821-1 - Efeito do exercício físico na nocicepção induzida no modelo de Doença de Parkinson em ratos
• Beneficiário: Karina Henrique Binda
• Modalidade de apoio: Bolsas no Brasil - Mestrado