Insulin-Dependent Maturation of Newly Generated Olfactory Sensory Neurons after Injury

Kuboki, Akihito; Kikuta, Seishi; Otori, Nobuyoshi; Kojima, Hiromi; Matsumoto, Ichiro; Reisert, Johannes; Yamasoba, Tatsuya

doi:10.1523/eneuro.0168-21.2021

Cited by 10 publications

(17 citation statements)

References 72 publications

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“…Methimazole disrupts the OE in a volume-dependent manner ( Kikuta et al, 2015 ). The dose used in this study was about half that used previously ( Kuboki et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…The fluid was taken into the nasal passage by the animal’s natural inhalation. This process was repeated three times daily, resulting in the delivery of a total of 90 μl insulin solution or saline, as previously described ( Kuboki et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Their nasal tissues, including the OE, were decalcified using 10% EDTA solution, pH 7.0, and then embedded in paraffin. Coronal sections (4 μm thick) were prepared and mounted on silane-coated slides, deparaffinized, and then autoclaved for 10 min in Target Retrieval Solution (S1700; Dako, Santa Clara, CA, United States) for antigen retrieval ( Kikuta et al, 2015 ; Kuboki et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…Insulin is also present in nasal mucus and influences the maturation and activity of individual OSNs through insulin receptor-mediated signaling ( Henkin, 2010 ; Kuboki et al, 2021 ). Further, the apoptotic wave that occurs after interruption of the neuronal connections between the OE and the olfactory bulb following bulbectomy is impaired by intranasal insulin administration ( Lacroix et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

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Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Kikuta

Kuboki

Yamasoba

2021

Front. Neural Circuits

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Insulin is present in nasal mucus and plays an important role in the survival and activity of individual olfactory sensory neurons (OSNs) via insulin receptor-mediated signaling. However, it is unclear whether insulin acts prophylactically against olfactotoxic drug-induced olfactory epithelium (OE) injury, and whether the degree of damage is affected by the concentration of insulin in the nasal mucus. The apoptosis-inducing drug methimazole was administered to the nasal mucus of diabetic and normal mice along with different concentrations of insulin. Immunohistochemical analysis was used to assess the relationship between damage to the OE and the mucus insulin concentration and the protective effect of insulin administration against eosinophilic cationic protein (ECP)-induced OE injury. Diabetic mice had lower concentrations of insulin in their nasal mucus than normal mice (diabetic vs. normal mice, p < 0.001). Methimazole administration reduced the number of OSNs in normal mice and had a more marked effect in diabetic mice. However, unilateral insulin administration prevented the methimazole-induced reduction in the number of OSNs on the ipsilateral side but not on the contralateral side (OSNs; Insulin vs. contralateral side, p < 0.001). Furthermore, intranasal ECP administration damaged the OE by inducing apoptosis (OSNs; ECP vs. contralateral side, p < 0.001), but this damage was largely prevented by insulin administration (OSNs; Insulin + ECP vs. contralateral side, p = 0.36), which maintained the number of mature OSNs. The severity of methimazole-induced damage to the OE is related to the insulin concentration in the nasal mucus (Correlation between the insulin concentration in nasal mucus and the numbers of OSNs, R2 = 0.91, p < 0.001), which may imply that nasal insulin protects OSNs and that insulin administration might lead to the development of new therapeutic agents for ECP-induced OE injury.

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“…Methimazole disrupts the OE in a volume-dependent manner ( Kikuta et al, 2015 ). The dose used in this study was about half that used previously ( Kuboki et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Kikuta

Kuboki

Yamasoba

2021

Front. Neural Circuits

Self Cite

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“…In actuality, chemosensory mechanisms hosted in different organs may be considered polymodal sensory systems that share some sensing molecules and transduction pathways. Olfactory neurons bear olfactory receptor proteins, yet they also express other receptors, for example, trace amine-associated receptors (TAARS) [ 2 ] and many receptors for hormones, to a large extent involved in metabolic regulation [ 3 , 4 , 5 ], but not limited to this function [ 6 ]. On the other hand, olfactory receptors are “ectopically” expressed at many sites [ 7 ] and contribute to various functions: In the pancreas, they modulate insulin release [ 8 ] and one olfactory receptor is involved in glucose metabolism [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Are Multiple Chemosensory Systems Accountable for COVID-19 Outcome?

Caretta

Mucignat‐Caretta

2021

JCM

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Chemosensory systems (olfaction, taste, trigeminus nerve, solitary chemoreceptor cells, neuroendocrine pulmonary cells, and carotid body, etc.) detect molecules outside or inside our body and may share common molecular markers. In addition to the impairment of taste and olfaction, the detection of the internal chemical environment may also be incapacitated by COVID-19. If this is the case, different consequences can be expected. (1) In some patients, hypoxia does not trigger distressing dyspnea (“silent” hypoxia): Long-term follow-up may determine whether silent hypoxia is related to malfunctioning of carotid body chemoreceptors. Moreover, taste/olfaction and oxygen chemoreceptors may be hit simultaneously: Testing olfaction, taste, and oxygen chemoreceptor functions in the early stages of COVID-19 allows one to unravel their connections and trace the recovery path. (2) Solitary chemosensory cells are also involved in the regulation of the innate mucosal immune response: If these cells are affected in some COVID-19 patients, the mucosal innate immune response would be dysregulated, opening one up to massive infection, thus explaining why COVID-19 has lethal consequences in some patients. Similar to taste and olfaction, oxygen chemosensory function can be easily tested with a non-invasive procedure in humans, while functional tests for solitary chemosensory or pulmonary neuroendocrine cells are not available, and autoptic investigation is required to ascertain their involvement.

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Sex steroid hormone synthesis, metabolism, and the effects on the mammalian olfactory system

Abaffy

Matsunami

2022

Cell Tissue Res

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Sex steroid hormones influence olfactory-mediated social behaviors, and it is generally hypothesized that these effects result from circulating hormones and/or neurosteroids synthesized in the brain. However, it is unclear whether sex steroid hormones are synthesized in the olfactory epithelium or the olfactory bulb, and if they can modulate the activity of the olfactory sensory neurons. Here, we review important discoveries related to the metabolism of sex steroids in the mouse olfactory epithelium and olfactory bulb, along with potential areas of future research. We summarize current knowledge regarding the expression, neuroanatomical distribution, and biological activity of the steroidogenic enzymes, sex steroid receptors, and proteins that are important to the metabolism of these hormones and reflect on their potential to influence early olfactory processing. We also review evidence related to the effects of sex steroid hormones on the development and activity of olfactory sensory neurons. By better understanding how these hormones are metabolized and how they act both at the periphery and olfactory bulb level, we can better appreciate the complexity of the olfactory system and discover potential similarities and differences in early olfactory processing between sexes.

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Insulin-Dependent Maturation of Newly Generated Olfactory Sensory Neurons after Injury

Cited by 10 publications

References 72 publications

Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Protective Effect of Insulin in Mouse Nasal Mucus Against Olfactory Epithelium Injury

Are Multiple Chemosensory Systems Accountable for COVID-19 Outcome?

Sex steroid hormone synthesis, metabolism, and the effects on the mammalian olfactory system

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