RT Journal Article
SR Electronic
T1 α-Synuclein pathology and reduced neurogenesis in the olfactory system affect olfaction in a mouse model of Parkinson’s disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.19.504562
DO 10.1101/2022.08.19.504562
A1 Eduardo Martin-Lopez
A1 D.J. Vidyadhara
A1 Teresa Liberia
A1 Sarah J. Meller
A1 Leah E. Harmon
A1 Ryan M. Hsu
A1 Kimberly Han
A1 Betül Yücel
A1 Sreeganga S. Chandra
A1 Charles A. Greer
YR 2022
UL http://biorxiv.org/content/early/2022/08/22/2022.08.19.504562.abstract
AB Parkinson’s Disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathological changes in the olfactory pathway of transgenic (Tg) mice expressing the human A30P mutant α-synuclein (α-syn) (α-syn-Tg mice) at 6-7 and 12-14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at 6-7 months, and OB periglomerular cells at 12-14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endo- and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12-14 months. Our data suggest that, 1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; 2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; 3) α-syn pathology is restricted to projection neurons in the olfactory pathway; 4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and 5) synaptic endo- and exocytosis defects in the OB may further explain olfactory deficits.Competing Interest StatementThe authors have declared no competing interest.