Abstract
Hyposmia 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 anterior olfactory nucleus, and then later affects other interconnected brain regions. Here, we bilaterally injected α-synuclein preformed fibrils into the olfactory bulbs of wild type male and female mice. Six months after injection, the anterior olfactory nucleus and 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. No overt impairments in the ability to engage in sniffing were evident in any group, suggesting preservation of the ability to coordinate respiration. At all-time points, females injected with fibrils exhibited reduced odor detection sensitivity, which was observed with the semi-automated plethysmography apparatus, but not a buried pellet test. In future studies, this sensitive methodology for assessing olfactory detection deficits could be used to define how α-synuclein pathology affects other aspects of olfactory perception and to clarify the neuropathological underpinnings of these deficits.
Highlights
Hyposmia is evident in over 90% of Parkinson’s disease (PD) patients
According to the Braak staging hypothesis, based on the analysis of post-mortem tissue from PD patients, α-synuclein pathology is initially present in the dorsal motor nucleus of the vagus, as well as the olfactory bulb (OB) and the anterior olfactory nucleus (AON)
The injection of preformed fibrils (PFFs) into the OB of wild type mice causes Lewy Body-like pathology, which propagates to synaptically connected brain regions over several months[16,17,18,19], including key olfactory areas implicated in odor perception
Summary
Hyposmia 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. At all-time points, females injected with fibrils exhibited reduced odor detection sensitivity, which was observed with the semi-automated plethysmography apparatus, but not a buried pellet test In future studies, this sensitive methodology for assessing olfactory detection deficits could be used to define how α-synuclein pathology affects other aspects of olfactory perception and to clarify the neuropathological underpinnings of these deficits. The injection of PFFs into the OB of wild type mice causes Lewy Body-like pathology, which propagates to synaptically connected brain regions over several months[16,17,18,19], including key olfactory areas implicated in odor perception These mice have been reported to develop progressive olfactory deficits for odor retention/memory and detection thresholds, using a testing set-up involving a cartridge containing a paper swab impregnated with odor[16]. These results, which sensitively and rigorously define odor detection sensitivity deficits following OB injections of PFFs, add to our understanding of the pathological mechanisms that might underlie olfactory deficits in PD
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