Difference between revisions of "Ehinger 2016 Mov Disord"

Latest revision as of 23:27, 29 February 2020

Ehinger JK, Morota S, Hansson MJ, Gesine P, Elmér E (2016) Mitochondrial respiratory function in peripheral blood cells from Huntington’s disease patients. Mov Disord doi:10.1002/mdc3.12308.

» [1]

Ehinger JK, Morota S, Hansson MJ, Gesine P, Elmer E (2016) Mov Disord

Abstract: Patients with Huntington’s disease display symptoms from both the central nervous system and peripheral tissues. Mitochondrial dysfunction has been implicated as part of the pathogenesis of the disease and has been reported in brain tissue and extracerebral tissues, such as muscle and blood cells, but the results are inconsistent. Therefore, the authors performed a refined evaluation of mitochondrial function in 2 types of peripheral blood cells from 14 patients with Huntington’s disease and 21 control subjects. Several hypotheses were predefined, including impaired mitochondrial complex II function (primary), complex I function (secondary), and maximum oxidative phosphorylation capacity (secondary) in patient cells.

High-resolution respirometry was applied to viable platelets and mononuclear cells. Data were normalized to cell counts, citrate synthase activity, and mitochondrial DNA copy numbers.

Normalized to citrate synthase activity, platelets from patients with Huntington’s disease displayed respiratory dysfunction linked to complex I, complex II, and lower maximum oxidative phosphorylation capacity. No difference was seen in mononuclear cells or when platelet data were normalized to cell counts or mitochondrial DNA. The ratio of complex I respiration through maximum oxidative phosphorylation was significantly decreased in patients compared with controls. The corresponding ratio for complex II was unaffected.

The data indicate decreased function of mitochondrial complex I in peripheral blood cells from patients with Huntington’s disease, although this could not be uniformly confirmed. The results do not confirm a systemic complex II dysfunction and do not currently support the use of mitochondrial function in blood cells as a biomarker for the disease. • Keywords: Huntington’s disease, Mitochondria, Blood cells, Respirometry, Oxygen consumption, PBMC

• O2k-Network Lab: JP Tokyo Uchino H, SE Lund Elmer E

Labels: MiParea: Respiration, Patients Pathology: Neurodegenerative

Organism: Human Tissue;cell: Blood cells, Lymphocyte, Platelet Preparation: Permeabilized cells, Intact cells

Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, S, CIV, NS, Other combinations, ROX HRR: Oxygraph-2k

2016-03, JP, SE, MitoEAGLE blood cells data

@@ Line 1: / Line 1: @@
 {{Publication
-|title=Ciammola A, Sassone J, Sciacco M, Mencacci NE, Ripolone M, Bizzi C, Colciago C, Moggio M, Parati G, Silani V, Malfatto G (2016) Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease. Mov Disord 26:130-7.
+|title=Ehinger JK, Morota S, Hansson MJ, Gesine P, Elmér E (2016) Mitochondrial respiratory function in peripheral blood cells from Huntington’s disease patients. Mov Disord doi:10.1002/mdc3.12308.
-|info=[http://www.ncbi.nlm.nih.gov/pubmed/20931633 PMID: 20931633 Open Access]
+|info=[http://onlinelibrary.wiley.com/doi/10.1002/mdc3.12308/abstract]
-|authors=Ciammola A, Sassone J, Sciacco M, Mencacci NE, Ripolone M, Bizzi C, Colciago C, Moggio M, Parati G, Silani V, Malfatto G
+|authors=Ehinger JK, Morota S, Hansson MJ, Gesine P, Elmer E
 |year=2016
 |journal=Mov Disord
-|abstract=Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the ''in vivo'' oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty-five HD subjects and twenty-five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed ''in vitro'' muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise.
+|abstract=Patients with Huntington’s disease display symptoms from both the central nervous system and peripheral tissues. Mitochondrial dysfunction has been implicated as part of the pathogenesis of the disease and has been reported in brain tissue and extracerebral tissues, such as muscle and blood cells, but the results are inconsistent. Therefore, the authors performed a refined evaluation of mitochondrial function in 2 types of peripheral blood cells from 14 patients with Huntington’s disease and 21 control subjects. Several hypotheses were predefined, including impaired mitochondrial complex II function (primary), complex I function (secondary), and maximum oxidative phosphorylation capacity (secondary) in patient cells.
+High-resolution respirometry was applied to viable platelets and mononuclear cells. Data were normalized to cell counts, citrate synthase activity, and mitochondrial DNA copy numbers.
+Normalized to citrate synthase activity, platelets from patients with Huntington’s disease displayed respiratory dysfunction linked to complex I, complex II, and lower maximum oxidative phosphorylation capacity. No difference was seen in mononuclear cells or when platelet data were normalized to cell counts or mitochondrial DNA. The ratio of complex I respiration through maximum oxidative phosphorylation was significantly decreased in patients compared with controls. The corresponding ratio for complex II was unaffected.
+The data indicate decreased function of mitochondrial complex I in peripheral blood cells from patients with Huntington’s disease, although this could not be uniformly confirmed. The results do not confirm a systemic complex II dysfunction and do not currently support the use of mitochondrial function in blood cells as a biomarker for the disease.
+|keywords=Huntington’s disease, Mitochondria, Blood cells, Respirometry, Oxygen consumption, PBMC
+|mipnetlab=JP Tokyo Uchino H, SE Lund Elmer E
 }}
 {{Labeling
-|area=Respiration, Exercise physiology;nutrition;life style, Patients
+|area=Respiration, Patients
+|diseases=Neurodegenerative
 |organism=Human
-|tissues=Skeletal muscle
+|tissues=Blood cells, Lymphocyte, Platelet
-|diseases=Neurodegenerative
+|preparations=Permeabilized cells, Intact cells
+|couplingstates=LEAK, ROUTINE, OXPHOS, ET
+|pathways=N, S, CIV, NS, Other combinations, ROX
 |instruments=Oxygraph-2k
-|additional=Labels, 2016-03
+|additional=2016-03, JP, SE, MitoEAGLE blood cells data,
 }}