TY  - JOUR
A1  - Pfeffer, Martina
A1  - Zimmermann, Zuzana
A1  - Gispert, Suzana
A1  - Auburger, Georg
A1  - Korf, Horst-Werner
A1  - Gall, Charlotte von
T1  - Impaired photic entrainment of spontaneous locomotor activity in mice overexpressing human mutant α-synuclein
T2  - International journal of molecular sciences
N2  - Parkinson’s disease (PD) is characterized by distinct motor and non-motor symptoms. Sleep disorders are the most frequent and challenging non-motor symptoms in PD patients, and there is growing evidence that they are a consequence of disruptions within the circadian system. PD is characterized by a progressive degeneration of the dorsal vagal nucleus and midbrain dopaminergic neurons together with an imbalance of many other neurotransmitters. Mutations in α-synuclein (SNCA), a protein modulating SNARE complex-dependent neurotransmission, trigger dominantly inherited PD variants and sporadic cases of PD. The A53T SNCA missense mutation is associated with an autosomal dominant early-onset familial PD. To test whether this missense mutation affects the circadian system, we analyzed the spontaneous locomotor behavior of non-transgenic wildtype mice and transgenic mice overexpressing mutant human A53T α-synuclein (A53T). The mice were subjected to entrained- and free-running conditions as well as to experimental jet lag. Furthermore, the vesicular glutamate transporter 2 (VGLUT2) in the suprachiasmatic nucleus (SCN) was analyzed by immunohistochemistry. Free-running circadian rhythm and, thus, circadian rhythm generation, were not affected in A53T mice. A53T mice entrained to the light–dark cycle, however, with an advanced phase angle of 2.65 ± 0.5 h before lights off. Moreover, re-entrainment after experimental jet lag was impaired in A53T mice. Finally, VGLUT2 immunoreaction was reduced in the SCN of A53T mice. These data suggest an impaired light entrainment of the circadian system in A53T mice.
KW  - Parkinson disease
KW  - endogenous clock
KW  - vesicular glutamate transporter 2
KW  - actography
KW  - circadian rhythms
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/47978
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-479783
SN  - 1422-0067
VL  - 19
IS  - 1651
SP  - 1
EP  - 13
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -