Deficits in olfactory sensitivity in a mouse model of Parkinson’s disease revealed by plethysmography of odor-evoked sniffing

Abstract

AbstractHyposmia is evident in over 90% of Parkinson’s disease (PD) patients. A characteristic of PD is intraneuronal deposits composed in part of α-synuclein fibrils. Based on the analysis of post-mortem PD patients, Braak and colleagues suggested that early in the disease α-synuclein pathology is present in the dorsal motor nucleus of the vagus, as well as the olfactory bulb and the anterior olfactory nucleus, and then later affects other interconnected brain regions. Here, we bilaterally injected α-synuclein preformed fibrils into the olfactory bulb of wild type male and female mice. Six-months after injection, the anterior olfactory nucleus and the piriform cortex displayed a high α-synuclein pathology load. We evaluated olfactory perceptual function by monitoring odor-evoked sniffing behavior in a plethysmograph at one-, three- and six-months after injection of α-synuclein fibrils. At all-time points, females injected with fibrils exhibited reduced odor detection sensitivity, which was detectable with the semi-automated plethysmography apparatus, but not a buried pellet test. In future studies, this sensitive methodology we used to assess olfactory detection deficits could be used to define how α-synuclein pathology affects other aspects of olfactory perception in PD models and to clarify the neuropathological underpinnings of these deficits.Highlights- α-synuclein pathology spreads through neuronally-connected areas after bilateral injection of preformed fibrils into the olfactory bulb.- A plethysmograph and an olfactometer were used for a semi-automated screen of odor-evoked sniffing as an assay for odor detection sensitivity.- Bilateral olfactory bulb injections of α-synuclein preformed fibrils in female mice led to reduced sensitivity for detecting odors.- The semi-automated plethysmography apparatus was more sensitive at detecting odor detection deficits than the buried pellet test.