Parkinson's Disease and Brain Mitochondrial Dysfunction: A Functional Phosphorus Magnetic Resonance Spectroscopy Study

Abstract

In spite of several evidences for a mitochondrial impairment in Parkinson's disease (PD), so far it has not been possible to show in vivo mitochondrial dysfunction in the human brain of PD patients. The authors used the high temporal and spatial resolution 31 phosphorus magnetic resonance spectroscopy ( 31 P MRS) technique, which they have previously developed in normal subjects and in patients with mitochondrial diseases to study mitochondrial function by observing high-energy phosphates (HEPs) and intracellular pH (pH) in the visual cortex of 20 patients with PD and 20 normal subjects at rest, during, and after visual activation. In normal subjects, HEPs remained unchanged during activation, but rose significantly (by 16%) during recovery, and pH increased during visual activation with a slow return to rest values. In PD patients, HEPs were within the normal range at rest and did not change during activation, but fell significantly (by 36%) in the recovery period; pH did not reveal a homogeneous pattern with a wide spread of values. Energy unbalance under increased oxidative metabolism requirements, that is, the postactivation phase, discloses a mitochondrial dysfunction that is present in the brain of patients with PD even in the absence of overt clinical manifestations, as in the visual cortex. This is in agreement with our previous findings in patients with mitochondrial disease without clinical central nervous system (CNS) involvement. The heterogeneity of the physicochemical environment (i.e., pH) suggests various degrees of subclinical brain involvement in PD. The combined use of MRS and brain activation is fundamental for the study of brain energetics in patients with PD and may prove an important tool for diagnostic purposes and, possibly, to monitor therapeutic interventions.

Myoinositol content in the human brain is modified by transcranial direct current stimulation in a matter of minutes: A 1H‐MRS study

“…MRI 3D T 1 (magnetization-prepared rapid gradient echo [MPRAGE]) and axial T 2 /proton density-weighted images were acquired and assessed under blinded conditions by an MRI expert (1,25,26). Single-voxel 1 H-MRS spectra both with and without water suppression were obtained from volumes of interest (8 ml) centered on the right motor cortex and the underlying white matter underneath the electrode, which in turn was localized by electrode landmarks.…”

“…No baseline correction was applied. Peak areas were obtained by the classic Levenberg-Marquardt frequency domain fitting method (1,25,26). Peak areas were calculated and absolute concentrations for NAA, mI, creatine (Cr), choline (Cho), and glutamate plus glutamine (Glx) (millimoles per kilogram) using the fully relaxed water signal as an internal standard of reference were also calculated (26,27), and thereafter data were converted as percent of baseline level for each subject.…”

Central Nervous System Imaging in Mitochondrial Disorders

“…Similar but less prominent alterations can be found in the grey matter 67 . The most frequent finding on MRS in MCD with CNS involvement is an increased lactate peak 15,18,33,65,[68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83] , which may precede the SLLs 15 . High levels of intra-ventricular lactate are usually associated with severe neurologic impairment 6 .…”

Cerebral Mitochondrial Metabolism in Early Parkinson's Disease

“…In vivo evidence of mitochondrial electron transport dysfunction has been inconsistent. Low ATP levels have been reported in the cerebral cortex in two studies (Piert et al, 1996;Rango et al, 2006). Overall cerebral oxygen metabolism has been reported to be not different from normal, but with relative increases in the basal ganglia opposite to the most symptomatic side Leenders et al, 1985).…”