TY  - JOUR
AU  - Neuner, Johanna
AU  - Filser, Severin
AU  - Michalakis, Stylianos
AU  - Biel, Martin
AU  - Herms, Jochen
TI  - A30P α-Synuclein interferes with the stable integration of adult-born neurons into the olfactory network.
JO  - Scientific reports
VL  - 4
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DZNE-2020-03591
SP  - 3931
PY  - 2014
AB  - Impaired olfaction is an early symptom in Parkinson disease (PD), although the exact cause is as yet unknown. Here, we investigated the link between PD-related mutant α-Synuclein (α-SYN) pathology and olfactory deficit, by examining the integration of adult-born neurons in the olfactory bulb (OB) of A30P α-SYN overexpressing mice. To this end, we chose to label one well-known vulnerable subpopulation of adult-born cells, the dopaminergic neurons. Using in vivo two-photon imaging, we followed the dynamic process of neuronal turnover in transgenic A30P α-SYN and wild-type mice over a period of 2.5 months. Our results reveal no difference in the number of cells that reach, and possibly integrate into, the glomerular layer in the OB. However, in mutant transgenic mice these new neurons have a significantly shortened survival, resulting in an overall reduction in the addition of neurons to the glomerular layer over time. We therefore propose unstable integration and impaired homeostasis of functional new neurons as a likely contributor to odour discrimination deficits in mutant α-SYN mice.
KW  - Animals
KW  - Dopamine: biosynthesis
KW  - Dopaminergic Neurons: diagnostic imaging
KW  - Lentivirus: genetics
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Transgenic
KW  - Olfaction Disorders: genetics
KW  - Olfactory Bulb: physiopathology
KW  - Parkinson Disease: diagnosis
KW  - Parkinson Disease: genetics
KW  - Protein Aggregation, Pathological: metabolism
KW  - Radiography
KW  - Smell: genetics
KW  - Smell: physiology
KW  - alpha-Synuclein: genetics
KW  - SNCA protein, human (NLM Chemicals)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Dopamine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24488133
C2  - pmc:PMC3909899
DO  - DOI:10.1038/srep03931
UR  - https://pub.dzne.de/record/137269
ER  -