Abstract
Olfactory dysfunction could be an early and reliable indicator for the diagnosis of neurodegenerative disorders such as Alzheimer and Parkinson's diseases. In this paper, we compare the potential of different noninvasive medical imaging modalities (optical coherence tomography, confocal microscopy, and fluorescence endomicroscopy) to distinguish how the olfactory epithelium, both at the cellular and the structural levels, is altered. Investigations were carried out on three experimental groups: two pathological groups (mice models with deliberately altered olfactory epithelium and Alzheimer's disease transgenic mice models) were compared with healthy mice models. As histological staining, the three tested noninvasive imaging tools demonstrated the general tubular organization of the olfactory epithelium on healthy mice. Contrary to OCT, confocal microscopy, and endomicroscopy allowed visualizing the inner structure of olfactory epithelium as well as its morphological or functional changes on pathological models, alterations classically observed with histological assessment. The results could lead to relevant development of imaging tools for noninvasive and early diagnosis of neurodegenerative diseases through the in situ characterization of the olfactory epithelium.
Highlights
IntroductionRecent studies have shown a strong correlation between impaired olfactory perception of patients and neurodegenerative conditions, such as Alzheimer’s disease (AD) (Arnold et al, 1998; Wang et al, 2010; Wesson et al, 2010; Kjelvik et al, 2014), Parkinson’s disease (Berg, 2008; Doty, 2012), frontotemporal dementia (McLaughlin and Westervelt, 2008; Alves et al, 2014), and Huntington’s disease (Lazic et al, 2007; Barresi et al, 2012)
The confocal microscopy device, which provided a higher resolution compared to Optical Coherence Tomography (OCT), allowed to visualize both the general shape of the turbinates and the inner structure of the olfactory epithelium (OE) tissues, and to measure its thicknesses (≈ 140 μm)
Images produced during optical microscopic characterization (Figure 3F) and the confocal microscopy examination (Figure 3G) were substantially identical and highlight the relevant use of confocal microscopy to explore and characterize OE tissue samples
Summary
Recent studies have shown a strong correlation between impaired olfactory perception of patients and neurodegenerative conditions, such as Alzheimer’s disease (AD) (Arnold et al, 1998; Wang et al, 2010; Wesson et al, 2010; Kjelvik et al, 2014), Parkinson’s disease (Berg, 2008; Doty, 2012), frontotemporal dementia (McLaughlin and Westervelt, 2008; Alves et al, 2014), and Huntington’s disease (Lazic et al, 2007; Barresi et al, 2012). In AD, odor detection, discrimination and identification are affected earlier than cognitive performances as demonstrated in several studies on patients (Talamo et al, 1991; Arnold et al, 1998; Wang et al, 2010), as well as on different animal models, in particular mice (Sohrabi et al, 2012; Alvarado-Martínez et al, 2013; Wu et al, 2013) These functional olfactory alterations are probably due to early Amyloid-β peptide deposits in the olfactory epithelium (OE) leading to cellular apoptosis and a decrease of dendritic spine densities (Yao et al, 2017). Pending the design of this new system, we have implemented a series of experiments to the ability of the imaging tools to: (i) distinguish the structural shape of the OE on healthy mice by comparing the results with those using conventional histological assessment, and (ii) identify morphological alterations and early signs of degeneration using pathological mice models (ZnSO4 lesion, APPswe/PSEN1E9 mice model of AD)
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