PMID- 29865270
OWN - NLM
STAT- MEDLINE
DCOM- 20181017
LR  - 20230926
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 6
DP  - 2018 Jun 3
TI  - Impaired Photic Entrainment of Spontaneous Locomotor Activity in Mice 
      Overexpressing Human Mutant alpha-Synuclein.
LID - 10.3390/ijms19061651 [doi]
LID - 1651
AB  - 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 
      alpha-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 
      alpha-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.
FAU - Pfeffer, Martina
AU  - Pfeffer M
AD  - Institut fur Anatomie II, Fachbereich Medizin, Heinrich Heine Universitat, 
      Universitatsstr. 1, D-40225 Dusseldorf, Germany. 
      Martina.Pfeffer@med.uni-duesseldorf.de.
FAU - Zimmermann, Zuzana
AU  - Zimmermann Z
AD  - Dr. Senckenbergische Anatomie II, Fachbereich Medizin, Goethe-Universitat 
      Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. 
      Zuzana.Zimmermann@gmx.de.
FAU - Gispert, Suzana
AU  - Gispert S
AD  - Experimental Neurology, Department of Neurology, Goethe-Universitat Frankfurt, 
      Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. 
      Gispert-sanchez@em.uni-frankfurt.de.
FAU - Auburger, Georg
AU  - Auburger G
AD  - Experimental Neurology, Department of Neurology, Goethe-Universitat Frankfurt, 
      Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. 
      Auburger@em.uni-frankfurt.de.
FAU - Korf, Horst-Werner
AU  - Korf HW
AD  - Institut fur Anatomie I, Fachbereich Medizin, Heinrich Heine Universitat, 
      Universitatsstr. 1, D-40225 Dusseldorf, Germany. Korf@uni-duesseldorf.de.
FAU - von Gall, Charlotte
AU  - von Gall C
AD  - Institut fur Anatomie II, Fachbereich Medizin, Heinrich Heine Universitat, 
      Universitatsstr. 1, D-40225 Dusseldorf, Germany. 
      Charlotte.Gall@med.uni-duesseldorf.de.
LA  - eng
PT  - Journal Article
DEP - 20180603
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (SNCA protein, human)
RN  - 0 (alpha-Synuclein)
SB  - IM
MH  - Animals
MH  - *Circadian Clocks
MH  - *Disease Models, Animal
MH  - Gene Expression Regulation
MH  - *Locomotion
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation
MH  - Parkinson Disease/*metabolism/physiopathology
MH  - Photic Stimulation
MH  - *Synaptic Transmission
MH  - Up-Regulation
MH  - alpha-Synuclein/genetics/*physiology
PMC - PMC6032049
OTO - NOTNLM
OT  - Parkinson disease
OT  - actography
OT  - circadian rhythms
OT  - endogenous clock
OT  - vesicular glutamate transporter 2
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2018/06/06 06:00
MHDA- 2018/10/18 06:00
PMCR- 2018/06/01
CRDT- 2018/06/06 06:00
PHST- 2018/05/16 00:00 [received]
PHST- 2018/05/31 00:00 [revised]
PHST- 2018/06/01 00:00 [accepted]
PHST- 2018/06/06 06:00 [entrez]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2018/10/18 06:00 [medline]
PHST- 2018/06/01 00:00 [pmc-release]
AID - ijms19061651 [pii]
AID - ijms-19-01651 [pii]
AID - 10.3390/ijms19061651 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Jun 3;19(6):1651. doi: 10.3390/ijms19061651.