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

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.

Inhibiting the mitochondrial pyruvate carrier does not ameliorate synucleinopathy in the absence of inflammation or metabolic deficits

“…To examine olfactory function in mice, the buried pellet test was carried out as recently described by our laboratory in Johnson et al 16 . In short, the mice were fasted overnight starting three days prior to testing.…”

A novel automated morphological analysis of microglia activation using a deep learning assisted model

“…To determine if validating the microglia detection models to a similar standard will allow for the comparison of fully independent datasets, we compared the results of the viral infection dataset with PBS sham injected animals in the αSyn induced olfactory dysfunction dataset. Viral infections are known to cause inflammation and microglia activation in the CNS[28,33,34], while the intracranial injections of PBS in the olfactory bulb do not[35,36]. As predicted, the analysis results in each of these datasets fall within a similar range across all measures, with a clear separation of values between the two datasets that suggests microglia activation as a result of viral infection but not from the PBS sham injections (Figure 3A).…”

Inhibiting the mitochondrial pyruvate carrier does not ameliorate synucleinopathy in the absence of inflammation or metabolic deficits

“…To examine olfactory function in mice, the buried pellet test was carried out as recently described by our laboratory in Johnson et al 16 In short, the mice were fasted overnight starting three days prior to testing. Throughout the experiment, their body weight was monitored and mice who lost more than 10% of their original body weight were excluded from further fasting and from the experiment.…”