Neuroplastic changes in the olfactory bulb associated with nasal inflammation in mice

Abstract

Background: Rhinitis and rhinosinusitis are olfactory disorders caused by inflammation of the nasal passage and paranasal sinuses. Although patients with chronic rhinosinusitis have smaller olfactory bulbs (OBs), there is limited knowledge regarding the influence of chronic nasal inflammation on OB neurons. Objective: Repeated intranasal administration of LPS that induced persistent nasal inflammation in mice caused a loss of olfactory sensory neurons (OSNs) and gliosis and synaptic loss in the OBs within 3 weeks. The present study aimed to clarify the effects of long-term LPS treatment on the OB neurocircuit. Methods: LPS was repeatedly administered into a mouse nostril for up to 24 weeks. For the recovery analyses, the mice received LPS for 10 weeks and were subsequently maintained without additional treatment for another 10 weeks. The effects of these treatments on the OBs were examined histologically. Three or more mice were analyzed per group. Results: Long-term repeated LPS administration caused OB atrophy, particularly in the layers along which OSN axons travel and in the superficial external plexiform layer, in which tufted cells form synapses with interneurons. Interestingly, the OBs recovered from atrophy after cessation of LPS administration: OB volume and superficial external plexiform layer thickness returned to pretreatment levels after the nontreatment period. In contrast, OSN regeneration was incomplete. Conclusion: These results suggest that chronic nasal inflammation induces structural changes in a specific OB circuit related to tufted cells, whereas tufted cells retain a high degree of plasticity that enables recovery from structural damages after inflammation subsides.

Increased lipopolysaccharide content is positively correlated with glucocorticoid receptor‐beta expression in chronic rhinosinusitis with nasal polyps

“…15 In animal models, instilling LPS into the nasal cavity of rats or mice can induce not only acute sinusitis but also the development of CRSwNP and olfactory dysfunction. 13,19,20 These findings further confirmed that noninfectious inflammatory factors were involved in the occurrence and development of inflammatory diseases. Although previous studies have shown that a certain amount of G − bacteria are present in CRSwNP, the expression and distribution of LPS in CRSwNP have not been investigated.…”

“…Purified LPS is a noninfectious inflammatory factor and can regulate the release of inflammatory mediators, resulting in chronic rhinosinusitis 15 . In animal models, instilling LPS into the nasal cavity of rats or mice can induce not only acute sinusitis but also the development of CRSwNP and olfactory dysfunction 13,19,20 . These findings further confirmed that noninfectious inflammatory factors were involved in the occurrence and development of inflammatory diseases.…”

Olfaction: Sensitive indicator of inflammatory burden in chronic rhinosinusitis

“…55,56 In rodents, recent studies suggest that persistent nasal inflammation induces glial activation, damage of the olfactory bulb circuit, and ultimately atrophy of the olfactory bulb. 86 Of particular interest, change in olfactory bulb volume is related to change in odor threshold, which is considered to partly reflect peripheral olfactory function. Given that olfactory bulb directly receives axons from the olfactory receptor neurons, the decrease of olfactory bulb volume in CRS might be due to decreasing input from the olfactory epithelium.…”

“…Reduced olfactory bulb volume has been demonstrated in CRS patients with smell loss 55,56 . In rodents, recent studies suggest that persistent nasal inflammation induces glial activation, damage of the olfactory bulb circuit, and ultimately atrophy of the olfactory bulb 86 . Of particular interest, change in olfactory bulb volume is related to change in odor threshold, which is considered to partly reflect peripheral olfactory function.…”

Intranasal Administration of Functionalized Soot Particles Disrupts Olfactory Sensory Neuron Progenitor Cells in the Neuroepithelium

“…The capacity for regeneration has limits and is reduced with aging or repeated insults (Child et al, 2018). Chronic nasal inflammation causes degeneration of olfactory neurons and their progenitor cells in both humans and animals (Chen et al, 2019;Hasegawa-Ishii et al, 2019). Insults that kill olfactory sensory neurons and their progenitor cells will lead to shrinkage and loss of the nasal 5 CSF outflow pathways.…”