Journal Article

DZNE-2020-03591

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A30P α-Synuclein interferes with the stable integration of adult-born neurons into the olfactory network.

Neuner, J. ; Filser, S.DZNE* ; Michalakis, S. ; Biel, M. ; Herms, J. (Last author)DZNE*

2014
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/srep03931

Abstract: 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.

Keyword(s): Animals (MeSH) ; Dopamine: biosynthesis (MeSH) ; Dopaminergic Neurons: diagnostic imaging (MeSH) ; Lentivirus: genetics (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Transgenic (MeSH) ; Olfaction Disorders: genetics (MeSH) ; Olfactory Bulb: physiopathology (MeSH) ; Parkinson Disease: diagnosis (MeSH) ; Parkinson Disease: genetics (MeSH) ; Protein Aggregation, Pathological: metabolism (MeSH) ; Radiography (MeSH) ; Smell: genetics (MeSH) ; Smell: physiology (MeSH) ; alpha-Synuclein: genetics (MeSH) ; SNCA protein, human ; alpha-Synuclein ; Dopamine

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Contributing Institute(s):

1. Ext Ludwig-Maximilians-University (Ext LMU)
2. Translational Brain Research (AG Herms)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2014

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