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  • Pathological consequences o...
    LaFever, Brandon J.; Kawasawa, Yuka Imamura; Ito, Ayako; Imamura, Fumiaki

    Brain, behavior, & immunity. Health, 05/2022, Volume: 21
    Journal Article

    Chronic olfactory inflammation (COI) in conditions such as chronic rhinosinusitis significantly impairs the functional and anatomical components of the olfactory system. COI induced by intranasal administration of lipopolysaccharide (LPS) results in atrophy, gliosis, and pro-inflammatory cytokine production in the olfactory bulb (OB). Although chronic rhinosinusitis patients have smaller OBs, the consequences of olfactory inflammation on OB neurons are largely unknown. In this study, we investigated the neurological consequences of COI on OB projection neurons, mitral cells (MCs) and tufted cells (TCs). To induce COI, we performed unilateral intranasal administration of LPS to mice for 4 and 10 weeks. Effects of COI on the OB were examined using RNA-sequencing approaches and immunohistochemical analyses. We found that repeated LPS administration upregulated immune-related biological pathways in the OB after 4 weeks. We also determined that the length of TC lateral dendrites in the OB significantly decreased after 10 weeks of COI. The axon initial segment of TCs decreased in number and in length after 10 weeks of COI. The lateral dendrites and axon initial segments of MCs, however, were largely unaffected. In addition, dendritic arborization and AIS reconstruction both took place following a 10-week recovery period. Our findings suggest that olfactory inflammation specifically affects TCs and their integrated circuitry, whereas MCs are potentially protected from this condition. This data demonstrates unique characteristics of the OBs ability to undergo neuroplastic changes in response to stress. •Early-stage chronic olfactory inflammation activates the ​interferon-γ-driven inflammatory pathways in the olfactory bulb.•Tufted cells undergo neurite dysregulation in response to chronic olfactory inflammation.•Mitral cells and interneurons in the external plexiform layer are largely unaffected by chronic olfactory inflammation.•Tufted cells experience complete recovery from neurite dysregulation following a period of ceased inflammation