Universität zu Köln

Hilker, Rueediger, Pilatus, Ulrich, Eggers, Carsten, Hagenah, Johann, Roggendorf, Julia, Baudrexel, Simon, Klein, Johannes C., Neumaier, Bernd ORCID: 0000-0001-5425-3116, Fink, Gereon R. ORCID: 0000-0002-8230-1856, Steinmetz, Helmuth, Klein, Christine and Hattingen, Elke ORCID: 0000-0002-8392-9004 (2012). The Bioenergetic Status Relates to Dopamine Neuron Loss in Familial PD with PINK1 Mutations. PLoS One, 7 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Mutations in the PINK1 gene cause autosomal recessive familial Parkinson's disease (PD). The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous (P-31) and proton (H-1) 3-T magnetic resonance spectroscopic imaging (MRSI) in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6) compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA) positron emission tomography (PET). The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and beta-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA K-i values correlated positively with MI (r = 0.879, p<0.001) and inversely with beta-ATP (r = -0.784, p = 0.008) and GPC concentrations (r = -0.651, p = 0.030) in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hilker, Rueediger UNSPECIFIED UNSPECIFIED UNSPECIFIED Pilatus, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Eggers, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Hagenah, Johann UNSPECIFIED UNSPECIFIED UNSPECIFIED Roggendorf, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Baudrexel, Simon UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Johannes C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED orcid.org/0000-0001-5425-3116 UNSPECIFIED Fink, Gereon R. UNSPECIFIED orcid.org/0000-0002-8230-1856 UNSPECIFIED Steinmetz, Helmuth UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hattingen, Elke UNSPECIFIED orcid.org/0000-0002-8392-9004 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-476837
DOI:	10.1371/journal.pone.0051308
Journal or Publication Title:	PLoS One
Volume:	7
Number:	12
Date:	2012
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MAGNETIC-RESONANCE SPECTROSCOPY; PARKINSONS-DISEASE; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE STRESS; BRAIN; MYOINOSITOL; RECOMMENDATIONS; METABOLISM; ASTROCYTES; GLUTAMATE Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47683