Effects of nasal inflammation on the olfactory bulb

Abstract

Sinonasal diseases, such as rhinosinusitis, affect up to 12% of individuals each year which constitutes these diseases as some of the most common medical conditions in the world. Exposure to environmental pathogens and toxicants via the nasal cavity can result in a severe inflammatory state commonly observed in these conditions. It is well understood that the epithelial and neuronal cells lining the olfactory mucosa, including olfactory sensory neurons (OSNs), are significantly damaged in these diseases. Prolonged inflammation of the nasal cavity may also lead to hyposmia or anosmia. Although various environmental agents induce inflammation in different ways via distinct cellular and molecular interactions, nasal inflammation has similar consequences on the structure and homeostatic function of the olfactory bulb (OB) which is the first relay center for olfactory information in the brain. Atrophy of the OB occurs via thinning of the superficial OB layers including the olfactory nerve layer, glomerular layer, and superficial external plexiform layer. Intrabulbar circuits of the OB which include connectivity between OB projection neurons, OSNs, and interneurons become significantly dysregulated in which synaptic pruning and dendritic retraction take place. Furthermore, glial cells and other immune cells become hyperactivated and induce a state of inflammation in the OB which results in upregulated cytokine production. Moreover, many of these features of nasal inflammation are present in the case of SARS-CoV-2 infection. This review summarizes the impact of nasal inflammation on the morphological and physiological features of the rodent OB.

Craniofacial and olfactory sensory changes after long-term unilateral nasal obstruction—an animal study using MMP-3-LUC transgenic rats

“…This result also explains the preservation of olfactory function through enhanced sensory inputs in previous studies 40 – 42 . The compensatory mechanism was established in previous research by Coppola et al; however, the result differs from evidence that sino-nasal diseases and pathogens cause degeneration of the olfactory epithelium 43 , primarily because of damage related to pathological conditions.…”

Persistent IL-6 expression is induced in the olfactory bulb of arthritis model mice before the onset of arthritis

“…These reports suggest that the early in ammatory changes in the OB observed in this study may have been the result of peripheral immunoin ammatory conditions being transmitted via the blood to the OB. Alternatively, in ammatory changes in the OB may occur via neurological inputs other than blood-derived inputs (19) (20). The presence of in ammation in the nasal cavity was reported to produce microglial activation in the OB via the olfactory nerve (19).…”

“…The presence of OB changes early in the pathology of arthritis suggests that it is a site prone to early abnormalities in response to particular immunoin ammatory conditions. In ammatory changes in the OB were reported to be induced by in ammation in the nose (19), but there are no reports of early and persistent elevations of IL-6 in the OB under other peripheral tissue in ammatory conditions. The early and persistent elevation of IL-6 in the OB under arthritic conditions that do not primarily target the nasal cavity suggests that the OB undergoes early in ammatory changes under certain peripheral immunoin ammatory conditions and that IL-6 may be involved in subsequent brain changes.…”

“…Alternatively, in ammatory changes in the OB may occur via neurological inputs other than blood-derived inputs (19) (20). The presence of in ammation in the nasal cavity was reported to produce microglial activation in the OB via the olfactory nerve (19). Furthermore, gamma-aminobutyric acid (GABA)-ergic neurons project to the OB from the basal forebrain (20), indicating abnormalities other than those of the OB may exist prior to those in the OB and cause in ammatory changes via neurons projecting to the OB.…”

Inhibition of endoplasmic reticulum stress prevents renal pathology in hindlimb unloaded mice

“…No previous report supporting this novel observation was found in previous literature. However, downstream consequences of elevated ER stress, including increased apoptosis and in ammation, can regulate the expression and function of olfactory sensors in other organs [27,28]. Together, these ndings exhibit a potential mechanistic interface between ER stress and olfactory transduction with relevance to renal injury.…”