Physical Training Regulates Mitochondrial Parameters and Neuroinflammatory Mechanisms in an Experimental Model of Parkinson’s Disease

Abstract EN

This study aimed to evaluate the effects of two different protocols for physical exercise (strength and aerobic training) on mitochondrial and inflammatory parameters in the 6-OHDA experimental model of Parkinson’s disease.

Six experimental groups were used (n=12 per group): untrained + vehicle (Sham), strength training + vehicle (STR), treadmill training + vehicle (TTR), untrained + 6-OHDA (U + 6-OHDA), strength training + 6-OHDA (STR + 6-OHDA), and treadmill training + 6-OHDA (TTR + 6-OHDA).

The mice were subjected to strength or treadmill training for 8 weeks.

PD was induced via striatal injection of 6-OHDA 24 h after the last exercise session.

Mice were euthanized by cervical dislocation and the striatum and hippocampus were homogenized to determine levels of tyrosine hydroxylase (TH), nuclear factor kappa B (NF-κB) p65, and sirtuin 1 (Sirt1) by western blot; tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-17, interferon-γ (IFN-γ), and transforming growth factor β1 (TGF-β1) levels by ELISA; NO content; and complex I (CI) activity.

STR + 6-OHDA mice had higher TH levels and CI activity and lower NF-κB p65 and IFN-γ levels in the striatum compared to U + 6-OHDA mice, while TTR + 6-OHDA mice had higher Sirt1 levels and CI activity in both the striatum and the hippocampus, compared to U + 6-OHDA mice.

Strength training increased CI activity and TH and Sirt1 levels and reduced NO, NF-κB p65, TNF-α, IFN-γ, IL-1β, and TGF-β1 levels in 6-OHDA mice, while treadmill exercise increased CI activity and NO, TH, and Sirt1 levels and reduced NF-κB p65, TNF-α, IFN-γ, and IL-1β levels.

Our results demonstrated that both treadmill training and strength training promote neuroprotection, possibly by stimulating Sirt1 activity, which may in turn regulate both mitochondrial function and neuroinflammation via deacetylation of NF-κB p65.

Changes in nitric oxide levels may also be a mechanism by which 6-OHDA-induced inflammation is controlled.