Research Paper Advance Articles
Treadmill intervention attenuates motor deficit with 6-OHDA-induced Parkinson’s disease rat via changes in lipid profiles in brain and muscle
- 1 School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
- 2 Department of Nutrition Science, Faculty of Medicine, Diponegoro University, Central Java, Indonesia
- 3 Department of Neurology, Taipei Medical University Hospital, Taipei 11031, Taiwan
- 4 School of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- 5 Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
- 6 Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
- 7 Department of Pathology, Taipei Medical University Hospital, Taipei 11031, Taiwan
- 8 Research Centre for Digestive Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan
- 9 Neuroscience Research Centre, Taipei Medical University, Taipei 11031, Taiwan
Received: January 2, 2024 Accepted: July 15, 2024 Published: January 3, 2025
https://doi.org/10.18632/aging.206181How to Cite
Copyright: © 2025 Panunggal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
One of the key hallmarks of Parkinson’s disease is the disruption of lipid homeostasis in the brain, which plays a critical role in neuronal membrane integrity and function. Understanding how treadmill training impacts lipid restructuring and its subsequent influence on motor function could provide a basis for developing targeted non-pharmacological interventions for individuals living with early stage of PD. This study aims to investigate the effects of a treadmill training intervention on motor deficits induced by 6-OHDA in rats model of PD. PD was induced by injecting 6-hydroxy dopamine (6-OHDA) into the medial forebrain bundle (MFB). For 10 weeks, rats underwent treadmill training on a four-lane motorized treadmill. Motor function deficits were evaluated through behavioral tests. Lipidomic analysis was performed through ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC MS/MS). Treadmill intervention significantly improved motor function and restored altered brain and muscle lipid profiles in PD rats. Among the lipid species identified in PD rats, brain abundance was highest for phosphatidylethanolamine (PE), correlating positively with the beam-walking scores; muscle abundance peaked with lysophosphatidylethanolamine (LysoPE), correlating positively with grip strength scores. In the brain, the levels of diacylglycerol (DG), triacylglycerol (TG), and lysophosphatidylcholine (PC) correlated positively with grip strength and rotarod scores, while only phosphatidylethanolamine (PE) linked to beam-walking scores. In the muscle, the levels of phosphatidylinositol (PI), lysophosphatidylethanolamine (PE), lysophosphatidic acid (PA), ceramide (Cer), and ganglioside were positively correlated with grip strength and rotarod scores. In conclusion, treadmill may protect the cortex, mitigating motor deficits via change lipid profiles in the brain and muscle.
Abbreviations
6-OHDA: 6-Hydroxydopamine; ALA: Alpha Linoleic Acid; BDNF: Brain-Derived Neurotrophic Factor; CE: Cholesterol Ester; CL: Cardiolipin; DA: Dopaminergic; DAT: Dopamine Transporter; DG: Diacylglycerol; DJ-1: Deglycase 1; FAHFA: Fatty Acyl of Hydroxyl Fatty Acid; FasL: Fas Ligand; GDNF: Glial cell-Derived Neurotrophic Factor; LA: Linoleic Acid; LBs: Lewy Bodies; LDL: Low-Density Lipoprotein; LysoPA: LysoPhosphatidic Acid; LysoPE: Lysophosphatidylethanolamine; LysoPC: Lysophosphatidylcholine; LRRK2: Leucine Rich Repeat Kinase 2; MFB: Medial Forebrain Bundle; MG: Monoacylglycerol; m(TOR): Nechanistic Target of the Rapamycin; NF-κB: Nuclear Factor Kappa-Light-Enhancer of Activated B Cells; Nrf2: Nuclear Factor Erythroid 2-Related Factor 2; TG: Triacylglycerol; PD: Parkinson’s disease; PA: Phosphatidic acid; PAGE: Polyacrylamide Gel Electrophoresis; PE: Phosphatidylethanolamine; PC: Phosphatidylcholine; PG: Phosphatidylglycerol; PIP: Phosphatidylinositol phosphate; PINK1: PATEN Induced Kinase 1; PS: Phosphatidylserine; PUFA: Polyunsaturated Fatty Acid; ROS: Reactive Oxygen Species; SFA: Saturated Fatty Acid; Sirt1: Sirtuin-1; SNPc: Substantia Nigra Pars Compacta; TH: Tyrosine Hydroxylase; TRAF2: TNF Receptor-Associated Factor 2; UPLC MS/MS: Liquid Chromatography-tandem Mass Spectrometry.