Universität zu Köln

Kinnerup, Martin B., Sommerauer, Michael, Damholdt, Malene F., Schaldemose, Jeppe L., Ismail, Rola, Terkelsen, Astrid J., Staer, Kristian, Hansen, Allan, Fedorova, Tatyana D., Knudsen, Karoline, Skjaerbaek, Casper ORCID: 0000-0003-2823-8785, Borghammer, Per ORCID: 0000-0001-6391-8052, Pavese, Nicola ORCID: 0000-0002-6801-6194, Brooks, David J. and Nahimi, Adjmal (2021). Preserved noradrenergic function in Parkinson's disease patients with rest tremor. Neurobiol. Dis., 152. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1095-953X

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Abstract

Noradrenergic neurotransmission may play an important role in tremor modulation through its innervation of key structures of the central tremor circuits. Here, Parkinson's disease (PD) patients with (PDT+) or without (PDT-) rest tremor had C-11-methylreboxetine(C-11-MeNER) positron emission tomography (PET) to test the hypothesis that noradrenaline terminal function was relatively preserved in PDT+ compared to PDT-. Methods: Sixty-five PD patients and 28 healthy controls (HC) were scanned with C-11-MeNER PET. Patients were categorized as PDT+ if subscores in UPDRS-III item 3 or MDS-UPDRS-III item 17 was >= 2; remaining were categorized as PDT-. Simplified reference tissue model 2 distribution volume ratios (DVR) for C-11-MeNER were calculated for thalamus, dorsal and median raphe, locus coeruleus (LC) and red nucleus using time activity curves (TACs) obtained from volumes of interest (VOI). Data were statistically interrogated with a general linear mixed model using 'region', and 'group' as factors and the interaction of 'region x group' was examined. Results: Tremor positive PD patients had a significantly higher mean C-11-MeNER DVR compared to PDT- in LC and thalamus. The PDT+ mean LC DVR was similar to that of HC. PDT+ mean C-11-MeNER DVRs were significantly lower than HC in the dorsal raphe while the PDT- group showed significantly lower mean C-11-MeNER DVR across all regions compared to HC. Conclusion: While both PD (T+) and PD (T-) groups showed a significant loss of noradrenaline terminal function compared to controls, noradrenergic neurons were relatively preserved in PDT+ in LC and thalamus. The greater loss of noradrenergic transporters in PDT- in LC and thalamus compared with PDT+ is in line with earlier in-vitro studies and could potentially contribute to their tremor negative phenotype.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kinnerup, Martin B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sommerauer, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Damholdt, Malene F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaldemose, Jeppe L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ismail, Rola UNSPECIFIED UNSPECIFIED UNSPECIFIED Terkelsen, Astrid J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Staer, Kristian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansen, Allan UNSPECIFIED UNSPECIFIED UNSPECIFIED Fedorova, Tatyana D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Knudsen, Karoline UNSPECIFIED UNSPECIFIED UNSPECIFIED Skjaerbaek, Casper UNSPECIFIED orcid.org/0000-0003-2823-8785 UNSPECIFIED Borghammer, Per UNSPECIFIED orcid.org/0000-0001-6391-8052 UNSPECIFIED Pavese, Nicola UNSPECIFIED orcid.org/0000-0002-6801-6194 UNSPECIFIED Brooks, David J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nahimi, Adjmal UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-591227
DOI:	10.1016/j.nbd.2021.105295
Journal or Publication Title:	Neurobiol. Dis.
Volume:	152
Date:	2021
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
Place of Publication:	SAN DIEGO
ISSN:	1095-953X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BRAIN Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59122