Browsing by Author "Merle, Laetitia"

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    Signatures for Viral Infection and Inflammation in the Proximal Olfactory System in Familial Alzheimer’s Disease
    (Elsevier, 2023) Bubak, Andrew N.; Merle, Laetitia; Niemeyer, Christy S.; Baxter, B. Dnate’; Gentile Polese, Arianna; Ramakrishnan, Vijay; Gomez, Johana; Madrigal, Lucia; Villegas-Lanau, Andres; Lopera, Francisco; Macklin, Wendy; Frietze, Seth; Nagel, Maria A.; Restrepo, Diego; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Alzheimer's disease (AD) is characterized by deficits in olfaction and olfactory pathology preceding diagnosis of dementia. Here we analyzed differential gene and protein expression in the olfactory bulb (OB) and tract (OT) of familial AD (FAD) individuals carrying the autosomal dominant presenilin 1 E280A mutation. Compared to control, FAD OT had increased immunostaining for β-amyloid (Aβ) and CD68 in high and low myelinated regions, as well as increased immunostaining for Iba1 in the high myelinated region. In FAD samples, RNA sequencing showed: (1) viral infection in the OB; (2) inflammation in the OT that carries information via entorhinal cortex from the OB to hippocampus, a brain region essential for learning and memory; and (3) decreased oligodendrocyte deconvolved transcripts. Interestingly, spatial proteomic analysis confirmed altered myelination in the OT of FAD individuals, implying dysfunction of communication between the OB and hippocampus. These findings raise the possibility that viral infection and associated inflammation and dysregulation of myelination of the olfactory system may disrupt hippocampal function, contributing to acceleration of FAD progression.
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    Transcriptional profiling reveals potential involvement of microvillous TRPM5-expressing cells in viral infection of the olfactory epithelium
    (Springer Nature, 2021-03-30) Baxter, B. Dnate’; Larson, Eric D.; Merle, Laetitia; Feinstein, Paul; Gentile Polese, Arianna; Bubak, Andrew N.; Niemeyer, Christy S.; Hassell, James, Jr.; Shepherd, Doug; Ramakrishnan, Vijay R.; Nagel, Maria A.; Restrepo, Diego; Otolaryngology -- Head and Neck Surgery, School of Medicine
    Background: Understanding viral infection of the olfactory epithelium is essential because the olfactory nerve is an important route of entry for viruses to the central nervous system. Specialized chemosensory epithelial cells that express the transient receptor potential cation channel subfamily M member 5 (TRPM5) are found throughout the airways and intestinal epithelium and are involved in responses to viral infection. Results: Herein we performed deep transcriptional profiling of olfactory epithelial cells sorted by flow cytometry based on the expression of mCherry as a marker for olfactory sensory neurons and for eGFP in OMP-H2B::mCherry/TRPM5-eGFP transgenic mice (Mus musculus). We find profuse expression of transcripts involved in inflammation, immunity and viral infection in TRPM5-expressing microvillous cells compared to olfactory sensory neurons. Conclusion: Our study provides new insights into a potential role for TRPM5-expressing microvillous cells in viral infection of the olfactory epithelium. We find that, as found for solitary chemosensory cells (SCCs) and brush cells in the airway epithelium, and for tuft cells in the intestine, the transcriptome of TRPM5-expressing microvillous cells indicates that they are likely involved in the inflammatory response elicited by viral infection of the olfactory epithelium.