Treadmill exercise modulates nigral and hippocampal cannabinoid receptor type 1 in the 6-OHDA model of Parkinson's disease

TY - JOUR

T1 - Treadmill exercise modulates nigral and hippocampal cannabinoid receptor type 1 in the 6-OHDA model of Parkinson's disease

AU - Henrique Binda, Karina

AU - Landau, Anne M

AU - Chacur, Marucia

AU - Brooks, David J

AU - Cristiano Real, Caroline

PY - 2023/9

Y1 - 2023/9

N2 - Physical exercise benefits Parkinson's disease (PD) patients but the mechanism is unclear. Cannabinoid receptor type 1 (CB1R) is known to be reduced in PD patients and animal models. We test the hypothesis that binding of the CB1R inverse agonist, [ 3H]SR141716A, is normalized by treadmill exercise in the toxin-induced 6-hydroxdopamine (6-OHDA) model of PD. Male rats had unilateral striatal injections of 6-OHDA or saline. After 15 days, half were submitted to exercise and half remained sedentary. [ 3H]SR141716A autoradiography was performed in postmortem tissue from striatum, substantia nigra (SN) and hippocampus. There was a 41% decrease of [ 3H]SR141716A specific binding in the ipsilateral SN of 6-OHDA-injected sedentary animals which was attenuated to 15% by exercise, when compared to saline-injected animals. No striatal differences were observed. A 30% bilateral hippocampal increase was observed in both healthy and 6-OHDA exercised groups. In addition, a positive correlation between nigral [ 3H]SR141716A binding and nociceptive threshold was observed in PD-exercised animals (p=0.0008), suggesting a beneficial effect of exercise in the pain associated with the model. Chronic exercise can reduce the detrimental effects of PD on nigral [ 3H]SR141716A binding, similar to the reported reduction after dopamine replacement therapy, so should be considered as an adjunct therapy for PD.

AB - Physical exercise benefits Parkinson's disease (PD) patients but the mechanism is unclear. Cannabinoid receptor type 1 (CB1R) is known to be reduced in PD patients and animal models. We test the hypothesis that binding of the CB1R inverse agonist, [ 3H]SR141716A, is normalized by treadmill exercise in the toxin-induced 6-hydroxdopamine (6-OHDA) model of PD. Male rats had unilateral striatal injections of 6-OHDA or saline. After 15 days, half were submitted to exercise and half remained sedentary. [ 3H]SR141716A autoradiography was performed in postmortem tissue from striatum, substantia nigra (SN) and hippocampus. There was a 41% decrease of [ 3H]SR141716A specific binding in the ipsilateral SN of 6-OHDA-injected sedentary animals which was attenuated to 15% by exercise, when compared to saline-injected animals. No striatal differences were observed. A 30% bilateral hippocampal increase was observed in both healthy and 6-OHDA exercised groups. In addition, a positive correlation between nigral [ 3H]SR141716A binding and nociceptive threshold was observed in PD-exercised animals (p=0.0008), suggesting a beneficial effect of exercise in the pain associated with the model. Chronic exercise can reduce the detrimental effects of PD on nigral [ 3H]SR141716A binding, similar to the reported reduction after dopamine replacement therapy, so should be considered as an adjunct therapy for PD.

KW - 6-OHDA

KW - Autoradiography

KW - Cannabinoid receptor type 1

KW - Parkinson's disease

KW - Treadmill exercise

UR - http://www.scopus.com/inward/record.url?scp=85161617810&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2023.148436

DO - 10.1016/j.brainres.2023.148436

M3 - Journal article

C2 - 37268248

SN - 0006-8993

VL - 1814

JO - Brain Research

JF - Brain Research

M1 - 148436

ER -