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Neuroinflammation results in dysfunctional mitral cells and olfactory impairment

ABSTRACT: Olfactory dysfunction is an underestimated symptom in multiple sclerosis (MS). Here, we examined the pathogenic mechanisms underlying inflammation-induced dysfunction of the olfactory bulb using the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Reduced olfactory function in EAE was associated with the degeneration of short-axon neurons, immature neurons, and mitral cells, together with their synaptic interactions and axonal repertoire. To dissect the mechanisms underlying the susceptibility of mitral cells, the main projection neurons of the olfactory bulb, we profiled their responses to neuroinflammation by single-nucleus RNA sequencing. Neuroinflammation resulted in the induction of potassium channel transcripts in mitral cells, which was reflected in reduced halothane-induced outward currents of these cells, likely contributing to the impaired olfaction in EAE animals.

ORGANISM(S): Mus musculus

PROVIDER: GSE268675 | GEO | 2024/12/31

REPOSITORIES: GEO

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Project description:Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future.

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Neuroinflammation results in dysfunctional mitral cells and olfactory impairment

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