Olfaction in Three Genetic and Two MPTP-Induced Parkinson’s Disease Mouse Models

Stefan Kurtenbach,Hermann Lübbert,Hanns Hatt,Sonja Wewering,Eva M Neuhaus,Alexander J Whitworth

doi:10.1371/journal.pone.0077509

Stefan Kurtenbach, Hermann Lübbert + Show 4 more

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https://doi.org/10.1371/journal.pone.0077509

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Abstract

Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson’s disease (PD) mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs) and an olfactory behavior test (cookie-finding test). We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and the most common disorder with motor deficits due to the degeneration of dopaminergic neurons in the substantia nigra [1]
Since signs of pathology can be found in the olfactory bulb at early stages [7], the impairments may be caused by beginning brain damage
In this study we investigated transgenic and toxin induced mouse models resembling some aspects of early stage PD pathology, to elucidate whether olfactory deficits are present and whether they originate in the olfactory epithelium (OE) or the brain

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and the most common disorder with motor deficits due to the degeneration of dopaminergic neurons in the substantia nigra [1]. Already at very early stages of PD, 70–95% of the patients exhibit deficits in odor detection and discrimination [10,11,12]. These olfactory deficits often precede motor symptoms by up to four years [13,14,15,16,17]. Of the six so-called Braak stages the Braak stage is already characterized by pathological changes in the olfactory bulb and anterior olfactory nucleus, maybe causing the patients’ olfactory deficits. Olfactory perception may serve as a tool for early diagnosis

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