Post mortem examination of Parkinson’s disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus.

Post mortem examination of Parkinson’s disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus.

Publication date: Mar 12, 2019

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most commonly used surgical treatment for Parkinson’s disease (PD). The disease-modifying aspects of DBS at a cellular level are not fully understood, and the key question of the effect of DBS on the degeneration of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) remains to be answered. A major technical hurdle in determining any neuroprotective effect by DBS is its use in mid- to late-stage patients with PD when a majority of the DA neurons have been lost. In this work, we hypothesized that the long-term clinical benefits of DBS are, at least in part, due to a neuromodulatory effect on the SNpc neurons. These changes would affect cellular energetics and mitochondrial metabolism. We examined the number and volume of mitochondria as well as their vicinity to the DA presynaptic terminals postmortem caudate and putamen of 3 healthy individuals, 4 PD cases, and 3 DBS-treated patients. PD seems to have caused an increase in the mean distance between mitochondria and presynaptic terminals as well as a decrease in mean mitochondrial volume and numbers in DA projections. Although there was no difference in distance between mitochondria and presynaptic terminals of SNpc neurons in PD brains vs. DBS-treated brains, DBS treatment seemed to have inhibited or reversed the reduction in mitochondrial volume and numbers caused by PD. These results suggest enhanced metabolic plasticity leading to neuroprotection in the SNpc as a result of STN-DBS.-Mallach, A., Weinert, M., Arthur, J., Gveric, D., Tierney, T. S., Alavian, K. N. Post mortem examination of Parkinson’s disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus.

Mallach, A., Weinert, M., Arthur, J., Gveric, D., Tierney, T.S., and Alavian, K.N. Post mortem examination of Parkinson’s disease brains suggests decline in mitochondrial biomass, reversed by deep brain stimulation of subthalamic nucleus. 20104. 2019 FASEB J.

Concepts Keywords
Biomass Substantia nigra
Caudate Putamen Neuron
DA Deep brain stimulation
DBS Neurological disorders
Deep Brain Stimulation Subthalamus
Dopaminergic Neurosurgical procedures
Energetics Subthalamic nucleus
FASEB Neurotechnology
Metabolism Medicine
Mitochondria Basal ganglia
Mitochondrial Branches of biology
Neuromodulatory Brain
Neurons Surgical treatment
Neuroprotection Deep brain stimulation
Neuroprotective PD disease
Parkinson
Plasticity
Postmortem
Presynaptic
Subthalamic Nucleus

Semantics

Type Source Name
pathway BSID Metabolism
gene UNIPROT EEF1A2
gene UNIPROT LRP2
gene UNIPROT MCF2L
gene UNIPROT SLC35G1

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