LaFever Brandon J, Kawasawa Yuka Imamura, Ito Ayako, Imamura Fumiaki
Department of Pharmacology, Penn State College of Medicine, 500 University Dr., Hershey, PA, 17033, USA.
Department of Biochemistry and Molecular Biology, Penn State College of Medicine, 500 University Dr., Hershey, PA, 17033, USA.
Brain Behav Immun Health. 2022 Mar 18;21:100451. doi: 10.1016/j.bbih.2022.100451. eCollection 2022 May.
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.
慢性鼻窦炎等病症中的慢性嗅觉炎症（COI）会显著损害嗅觉系统的功能和解剖结构。经鼻内给予脂多糖（LPS）诱导的COI会导致嗅球（OB）萎缩、胶质增生和促炎细胞因子产生。尽管慢性鼻窦炎患者的嗅球较小，但嗅觉炎症对嗅球神经元的影响在很大程度上尚不清楚。在本研究中，我们调查了COI对嗅球投射神经元、二尖瓣细胞（MCs）和簇状细胞（TCs）的神经学影响。为了诱导COI，我们对小鼠进行单侧鼻内给予LPS，持续4周和10周。使用RNA测序方法和免疫组织化学分析检查COI对嗅球的影响。我们发现，重复给予LPS 4周后，嗅球中与免疫相关的生物学途径上调。我们还确定，COI 10周后，嗅球中TC侧树突的长度显著缩短。COI 10周后，TC的轴突起始段数量和长度均减少。然而，MCs的侧树突和轴突起始段基本未受影响。此外，经过10周的恢复期后，树突分支和轴突起始段重建均发生。我们的研究结果表明，嗅觉炎症特异性地影响TCs及其整合电路，而MCs可能免受这种情况的影响。该数据证明了嗅球在应激反应中发生神经可塑性变化的独特特征。
