Differential Effects of Nasal Inflammation and Odor Deprivation on Layer-Specific Degeneration of the Mouse Olfactory Bulb

Hasegawa-Ishii, Sanae; Imamura, Fumiaki; Nagayama, Shin; Murata, M.; Shimada, Atsuyoshi

doi:10.1523/eneuro.0403-19.2020

Cited by 30 publications

(52 citation statements)

References 45 publications

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“…Mice were consistently housed in groups separated by gender. The intranasal administration was performed according to our previous study [6][7][8] . Briefly, the mice were anesthetized with isoflurane and 10-µL physiologic saline (saline-treated mice) or LPS from Escherichia coli O55:B5 (1 mg/mL; Sigma) (LPS-treated mice) was administered to bilateral nostrils three times per week for 9 weeks.…”

Section: Methodsmentioning

confidence: 99%

Sex-dependent differences in the gut microbiota following chronic nasal inflammation in adult mice

Mishima

Osaki

Shimada

et al. 2021

Sci Rep

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A growing body of evidence suggests a relationship between olfactory dysfunction and the pathogenesis of mental disorders. Our previous studies indicated that chronic nasal inflammation caused loss of olfactory sensory neurons and gross atrophy of the olfactory bulb, which may lead to olfactory dysfunction. Simultaneously, increasing numbers of reports have elucidated the importance of gut microbiota to maintain brain function and that dysbiosis may be associated with neuropsychiatric disorders. Here we examined whether chronic nasal inflammation perturbed gut microbiota and whether there were sex differences in this pattern. Eight-week-old C57BL/6 mice repeatedly received bilateral nasal administration of lipopolysaccharide (LPS) 3 times/week to cause chronic nasal inflammation or saline as a control. At 9 weeks, cecal feces were used for 16S metagenomic analysis and whole blood and fresh tissue of spleen were used for ELISA analyses. Microbiome analysis demonstrated a remarkable change of the gut microbiota in male mice with chronic nasal inflammation which was different from that in female mice. In both mice, systemic inflammation did not occur. This has shown for the first time that chronic nasal inflammation correlates with sex-dependent changes in the gut microbiota. The detailed mechanism and potential alteration to brain functions await further studies.

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Section: Methodsmentioning

confidence: 99%

Sex-dependent differences in the gut microbiota following chronic nasal inflammation in adult mice

Mishima

Osaki

Shimada

et al. 2021

Sci Rep

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“…administration of LPS causes dendritic retraction and axonal instability of TCs, but not MCs, in the mouse OB. The superficial OB layers (GL, ONL, sEPL) are the primary region of OB atrophy and inflammation at 10 weeks of LPS administrations 29,30 . Our results suggest that the reduction of dendrites that was observed in the ipsilateral OB is primarily attributed to a reduction in the sEPL.…”

Section: Discussionmentioning

confidence: 99%

“…For analyses of recovery, one group of eight-week-old +/Het mice (n=3) underwent unilateral 10week LPS administrations as discussed previously 23,29,30 and were subsequently housed for 10 weeks with no additional treatment. Three days prior to being sacrificed for immunohistochemical analyses, mice were intraperitoneally injected with tamoxifen (30 mg/kg).…”

Section: Animalsmentioning

confidence: 99%

“…The presence of proinflammatory cytokines such as IFN-γ and TNF-α are capable of causing dendritic atrophy, retraction, and loss of synapses in primary neuronal cultures 36 . It is important to note that LPS-induced COI does not cause the death of OB projection neurons (MCs/TCs) at any point up to the 24-week time point 23,29,30 . Therefore, we aimed to explore the potential phenomenon of dendritic retraction of MC/TCs following our COI paradigm.…”

Section: Reduction Of Tufted Cell Lateral Dendrites Following 10-week Coimentioning

confidence: 99%

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Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

LaFever

Kawasawa

Ito

et al. 2021

Preprint

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Background : 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 OB. Although chronic rhinosinusitis patients have smaller olfactory bulbs (OBs), the consequences of olfactory inflammation on OB neurons are largely unknown. Methods : In this study, we investigated the neurological consequence 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. Results : 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 axon initial segment reconstruction both took place following a 10-week recovery period. Conclusion : Our findings suggests 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.

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“…Gray matter volume within the primary and secondary olfactory cortices was also significantly increased 3 months after surgical treatment for CRS ( Güllmar et al, 2017 ; Whitcroft et al, 2018b ). Furthermore, an animal study demonstrated that neuroplastic changes in the olfactory bulb were directly associated with nasal inflammation ( Hasegawa-Ishii et al, 2019 ) and loss of olfactory sensory neuronal activity rather than neuroinflammation in the olfactory bulb was the major cause of inflammation-induced olfactory bulb atrophy ( Hasegawa-Ishii et al, 2020 ). It can be inferred that controlled nasal inflammation by surgical procedure or medical treatment contributes to the improvement of peripheral olfactory function and subsequent recovery of the olfactory bulb volume and gray matter volume.…”

Section: Clinically Meaningful Classification Of Olfactory Dysfunctiomentioning

confidence: 99%

Clinical Implications of Psychophysical Olfactory Testing: Assessment, Diagnosis, and Treatment Outcome

Bleier

Wei

et al. 2021

Front. Neurosci.

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Purpose of ReviewOlfactory dysfunction dramatically impairs quality of life with a prevalence of 20% in the general adult population. Psychophysical olfactory testing has been widely used to evaluate the ability to smell due to its validated utility and feasibility in clinic. This review summarizes the current literature regarding psychophysical olfactory testing and the clinical relevance of the olfactory testing with different components. Furthermore, the review highlights the diagnosis and treatment value of olfactory subtests in patients with olfactory dysfunction.Recent FindingsWith the accumulation of studies of psychophysical olfactory testing in olfactory disorders, the clinical relevance of olfactory testing with different components is expanding. Different olfactory domains present with distinct olfactory processing and cortical activity. Psychophysical assessment of olfaction with three domains reveals different levels of olfactory processing and might assist with analyzing the pathophysiologic mechanism of the various olfactory disorders. Furthermore, olfactory thresholds provided the largest amount of non-redundant information to the olfactory diagnosis. Sinonasal olfactory dysfunction and non-sinonasal-related olfactory dysfunction are emerging classifications of smell disorders with certain characteristics of olfactory impairment and different responses to the therapy including steroids, sinus surgery, and olfactory training.SummaryThese recent advancements should promote the understanding of psychophysical olfactory testing, the association between individual subcomponents and neurophysiological processes, and pave the way for precision assessment and treatment of the olfactory dysfunction.

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Differential Effects of Nasal Inflammation and Odor Deprivation on Layer-Specific Degeneration of the Mouse Olfactory Bulb

Cited by 30 publications

References 45 publications

Sex-dependent differences in the gut microbiota following chronic nasal inflammation in adult mice

Sex-dependent differences in the gut microbiota following chronic nasal inflammation in adult mice

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

Clinical Implications of Psychophysical Olfactory Testing: Assessment, Diagnosis, and Treatment Outcome

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