Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson's Disease.
Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA), or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes) were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0) and LPC (18:1), which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.
Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada. kyle_farmer@carleton.ca.
Kyle
K
Farmer
Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada. csmith@connect.carleton.ca.
Catherine A
CA
Smith
Carleton University Department of Neuroscience, 1125 Colonel By Drive, Life Sciences Research Building, Ottawa, ON K1S 5B6, Canada. shawn_hayley@carleton.ca.
Shawn
S
Hayley
Carleton University Department of Chemistry and Institute of Biochemistry, 1125 Colonel By Drive, Steacie Building, Ottawa, ON K1S 5B6, Canada. jeff_smith@carleton.ca.
Jeffrey
J
Smith
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D050356:Lipid Metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008297:Male; D010300:Parkinson Disease / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D013378:Substantia Nigra / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines
6-hydroxydopamine; HPLC-ESI-MS/MS; Parkinson’s disease; early stage model; lipidomic profile