Universität zu Köln

Kordys, Elena, Apetz, Nadine, Schneider, Katharina, Duncan, Eilidh, Bueschbell, Beatriz ORCID: 0000-0001-6777-0032, Rohleder, Cathrin ORCID: 0000-0002-3559-1846, Sue, Michael, Drzezga, Alexander, Neumaier, Bernd, Timmermann, Lars and Endepols, Heike ORCID: 0000-0002-6166-4818 (2017). Motor impairment and compensation in a hemiparkinsonian rat model: correlation between dopamine depletion severity, cerebral metabolism and gait patterns. EJNMMI Res., 7. S. 1 - 12. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 2191-219X

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Abstract

Background: In Parkinson's disease (PD), cerebral dopamine depletion is associated with PD subtype-specific metabolic patterns of hypo- and hypermetabolism. It has been hypothesised that hypometabolism reflects impairment, while hypermetabolism may indicate compensatory activity. In order to associate metabolic patterns with pathophysiological and compensatory mechanisms, we combined resting state [F-18]FDG-PET (to demonstrate brain metabolism in awake animals), [F-18]FDOPA-PET (dopamine depletion severity) and gait analysis in a unilateral 6-hydroxydopamine rat model. Results:We found unilateral nigro-striatal dopaminergic loss to decrease swing speed of the contralesional forelimb and stride length of all paws in association with depletion severity. Depletion severity was found to correlate with compensatory changes such as increased stance time of the other three paws and diagonal weight shift to the ipsilesional hind paw. [F-18]FDG-PET revealed ipsilesional hypo- and contralesional hypermetabolism; metabolic deactivation of the ipsilesional network needed for sensorimotor integration (hippocampus/retrosplenial cortex/lateral posterior thalamus) was solely associated with bradykinesia, but hypometabolism of the ipsilesional rostral forelimb area was related to both pathological and compensatory gait changes. Mixed effects were also found for hypermetabolism of the contralesional midbrain locomotor region, while contralesional striatal hyperactivation was linked to motor impairments rather than compensation. Conclusions: Our results indicate that ipsilesional hypo- and contralesional hypermetabolism contribute to both motor impairment and compensation. This is the first time when energy metabolism, dopamine depletion and gait analysis were combined in a hemiparkinsonian model. By experimentally increasing or decreasing compensational brain activity, its potential and limits can be further investigated.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kordys, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Apetz, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Duncan, Eilidh UNSPECIFIED UNSPECIFIED UNSPECIFIED Bueschbell, Beatriz UNSPECIFIED orcid.org/0000-0001-6777-0032 UNSPECIFIED Rohleder, Cathrin UNSPECIFIED orcid.org/0000-0002-3559-1846 UNSPECIFIED Sue, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmermann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Endepols, Heike UNSPECIFIED orcid.org/0000-0002-6166-4818 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221530
DOI:	10.1186/s13550-017-0317-9
Journal or Publication Title:	EJNMMI Res.
Volume:	7
Page Range:	S. 1 - 12
Date:	2017
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	2191-219X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PARKINSONS-DISEASE; NETWORK ACTIVITY; BASAL GANGLIA; HIPPOCAMPAL-FORMATION; RETROSPLENIAL CORTEX; MECHANISMS; BRAIN; PET Multiple languages Radiology, Nuclear Medicine & Medical Imaging Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22153