K H Binda1, T P Lillethorup2, C C Real3, S L Bærentzen4, M N Nielsen5, D Orlowski6, D J Brooks7, M Chacur8, A M Landau9. 1. Translational Neuropsychiatry Unit, Aarhus University, Universitetsbyen 13, Building 2b, Aarhus C 8000, Denmark; Department of Nuclear Medicine and PET, Aarhus University and Hospital, Palle Juul-Jensens Boulevard 165, J109, Aarhus N 8200, Denmark; Laboratory of Functional Neuroanatomy of Pain, Departamento de Anatomia, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: karina.binda@clin.au.dk. 2. Department of Nuclear Medicine and PET, Aarhus University and Hospital, Palle Juul-Jensens Boulevard 165, J109, Aarhus N 8200, Denmark. Electronic address: thealillethorup@clin.au.dk. 3. Translational Neuropsychiatry Unit, Aarhus University, Universitetsbyen 13, Building 2b, Aarhus C 8000, Denmark; Department of Nuclear Medicine and PET, Aarhus University and Hospital, Palle Juul-Jensens Boulevard 165, J109, Aarhus N 8200, Denmark; Laboratory of Nuclear Medicine (LIM 43), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: caroline.real@clin.au.dk. 4. Translational Neuropsychiatry Unit, Aarhus University, Universitetsbyen 13, Building 2b, Aarhus C 8000, Denmark; Department of Nuclear Medicine and PET, Aarhus University and Hospital, Palle Juul-Jensens Boulevard 165, J109, Aarhus N 8200, Denmark. Electronic address: slb@clin.au.dk. 5. Translational Neuropsychiatry Unit, Aarhus University, Universitetsbyen 13, Building 2b, Aarhus C 8000, Denmark. Electronic address: marit.nielsen@clin.au.dk. 6. Center for Experimental Neuroscience (CENSE), Department of Clinical Medicine, Aarhus University and Department of Neurosurgery, Aarhus University Hospital, Aarhus N, 8200, Denmark. Electronic address: dorl@clin.au.dk. 7. Department of Nuclear Medicine and PET, Aarhus University and Hospital, Palle Juul-Jensens Boulevard 165, J109, Aarhus N 8200, Denmark; Institute for Translational and Clinical Research, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. Electronic address: dbrooks@clin.au.dk. 8. Laboratory of Functional Neuroanatomy of Pain, Departamento de Anatomia, Universidade de Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: chacurm@icb.usp.br. 9. Translational Neuropsychiatry Unit, Aarhus University, Universitetsbyen 13, Building 2b, Aarhus C 8000, Denmark; Department of Nuclear Medicine and PET, Aarhus University and Hospital, Palle Juul-Jensens Boulevard 165, J109, Aarhus N 8200, Denmark. Electronic address: alandau@clin.au.dk.
Abstract
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 μ-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 μ-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 μ-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.
BACKGROUND:Parkinson's disease (PD) is characterized by Lewy body and neurite pathology associated with dopamineterminal dysfunction. Clinically, it is associated with motor slowing, rigidity, and tremor. Postural instability and pain are also features. Physical exercise benefits PDpatients - possibly by promoting neuroplasticity including synaptic regeneration. OBJECTIVES: In a parkinsonianrat model, we test the hypotheses that exercise: (a) increases synaptic density and reduces neuroinflammation and (b) lowers the nociceptive threshold by increasing μ-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 μ-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 μ-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.
Authors: Monika Zawadka-Kunikowska; Jacek J Klawe; Małgorzata Tafil-Klawe; Monika Bejtka; Łukasz Rzepiński; Mirosława Cieślicka Journal: Int J Environ Res Public Health Date: 2022-10-04 Impact factor: 4.614