Parkinson’s disease and energy metabolism: investigation of polymorphonuclear (PMN) cells by nuclear magnetic resonance(NMR) spectroscopy

Abstract

Background: Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Currently available treatment relieves the symptoms, but the disease progress is unaffected. PD is best known for its effects on the central nervous system (CNS), but affects the periphery as well. The cause is unknown, except in genetically-determined cases, but there is substantial evidence to implicate mitochondria and energy metabolism in PD pathophysiology.

Purpose of the study: Our hypothesis was that the energy metabolism of brain cells might be reflected in mitochondrial function of circulating blood cells such as polymorphonuclear(PMN) leukocytes. The main purpose of this study was to develop a method to investigate energy metabolism in PMN.

Methods: Isolated PMN from six PD patients and six matched controls were incubated inculture medium with glucose as an energy source ([U-¹³C]Glc or ¹²C-Glc). PMN extractswere subsequently analysed by ¹³C- NMR and ³¹P-NMR spectroscopy.

Results: ¹³C- NMR spectroscopy displayed strong signals from glucose and lactate, whichindicated glycolytic activity, in addition to other weaker signals. Energy metabolism was alsodemonstrated by ³¹P-NMR spectra, which displayed strong signals for the high energy phosphates ATP and ADP. Quantification of the two substances proved PMN recovering inthe culture, achieving a relatively high ATP/ADP ratio. However, no significant difference inthe ATP/ADP ratio between patients with PD and healthy controls was found.

Conclusion: PMN survive isolation and demonstrate metabolic activity, achieving a relativelyhigh ATP to ADP ratio. ¹³C- NMR and ³¹P-NMR spectroscopy both proved to be usefulmeans for investigation of energy metabolism in PMN. Even though clear differences inenergy metabolism in PMN between cells isolated from patients with PD and healthy controlscould not be obtained due to the limited number of experiments conducted, a broader insightto methodological aspects for investigation of energy metabolism has been provided by thepresent study.