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

J Allergy Clin Immunol. 2019 Mar;143(3):978-989.e3. doi: 10.1016/j.jaci.2018.09.028. Epub 2018 Oct 10.


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.

Keywords: Chronic rhinosinusitis; LPS; brain plasticity; nasal inflammation; olfactory system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Inflammation / pathology
  • Interneurons / drug effects
  • Lipopolysaccharides / administration & dosage*
  • Male
  • Mice
  • Nasal Cavity / pathology
  • Neuronal Plasticity / drug effects*
  • Olfactory Bulb / drug effects*
  • Olfactory Bulb / pathology
  • Sensory Receptor Cells / drug effects
  • Synapses / drug effects


  • Lipopolysaccharides