Impaired Formation of Primary Cilia in Olfactory Neuronal Precursors Is Associated with Decreased Proliferation and Maturation in Individuals with Hyposmia

TL;DR

Impaired formation of primary cilia in olfactory neurons is linked to reduced cell growth and maturation in people with a diminished sense of smell.

Contribution

This study identifies a novel link between primary cilia dysfunction and olfactory impairment in hyposmic individuals.

Findings

Hyposmic individuals show reduced frequency and shorter length of primary cilia in olfactory neuronal precursors.

Olfactory neuronal precursors from hyposmic individuals exhibit decreased proliferation and differentiation.

Defects in cilia formation may hinder the maturation of olfactory sensory neurons.

Abstract

Smell dysfunction affects quality of life and is considered an early clinical sign of Alzheimer’s and Parkinson’s diseases. Olfactory loss increases with age and is associated with certain ciliopathies, a group of genetic disorders characterized by a wide spectrum of multisystemic disturbances. The dysfunction of mature olfactory sensory neurons (OSNs) in the olfactory neuronal pathway remains poorly understood. Previous evidence suggests that primary cilia proteins are involved in the maturation of olfactory sensory neurons (OSNs). In this study, we obtained olfactory neuronal precursors (ONPs) from the olfactory mucosa of young and older healthy volunteers who reported smell impairment (hyposmia) without neurological deficits or underlying airflow issues (conductive olfactory loss) and from normosmic individuals. In vitro analysis of ONPs showed that these cells can form primary cilia in normosmic individuals, while in hyposmic participants, there is a reduction in cilia frequency and a shorter length. In addition, ONPs from hyposmic individuals had a decrease in proliferation and cell differentiation. Our data indicate that alterations in molecular pathways related to primary cilia formation and the proliferation of ONPs lead to defects in neuronal maturation. These changes may hinder the differentiation of olfactory sensory neurons OSNs and contribute, at least in part, to olfactory loss.

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