scholarly journals Insulin-dependent maturation of newly generated olfactory sensory neurons after injury

2021 ◽  
Author(s):  
Akihito Kuboki ◽  
Shu Kikuta ◽  
Nobuyoshi Otori ◽  
Hiromi Kojima ◽  
Ichiro Matsumoto ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Sensory Neurons ◽  
Pancreatic Beta Cells ◽  
Enriched Environment ◽  
Receptor Expression ◽  
Olfactory Sensory Neurons ◽  
Diabetic Mice ◽  
Insulin Levels ◽  
Intranasal Application ◽  
And Control

AbstractLoss of olfactory sensory neurons (OSNs) after injury to the olfactory epithelium (OE) triggers the generation of OSNs that are incorporated into olfactory circuits to restore olfactory sensory perception. This study addresses how insulin receptor-mediated signaling affects the functional recovery of OSNs after OE injury. Insulin levels were reduced in mice by ablating the pancreatic beta cells via streptozotocin injections. These streptozotocin-induced diabetic and control mice were then intraperitoneally injected with the olfactotoxic drug methimazole to selectively ablate OSNs. The OE of diabetic and control mice regenerated similarly until day 14 after injury. Thereafter, the OE of diabetic mice contained fewer mature and more apoptotic OSNs than control mice. Functionally, diabetic mice showed reduced electro-olfactogram responses and their olfactory bulbs had fewer c-Fos-active cells following odor stimulation, as well as performed worse in an odor-guided task compared to control mice. Insulin administered intranasally during day 8 to 13 after injury was sufficient to rescue recovery of OSNs in diabetic mice compared to control levels, while insulin administration between days 1 – 6 did not. During this critical time window on day 8 – 13 after injury, insulin receptors are highly expressed and intranasal application of insulin receptor antagonist inhibits regeneration. Furthermore, an insulin-enriched environment could facilitate regeneration even in non-diabetic mice. These results indicate that insulin facilitates the regeneration of OSNs after injury and suggest a critical stage during recovery (8 – 13 days after injury) during which the maturation of newly generated OSNs is highly dependent on and promoted by insulin.Significance StatementAlthough insulin receptor signaling is known to influence on cellular processes such as proliferation and apoptosis, it is poorly understood whether the insulin influences the regeneration of olfactory sensory neurons (OSNs) after injury. We compared the maturation processes of new OSNs after the methimazole-induced loss of pre-existing OSNs between diabetic and control mice. The results show that the regeneration of new OSNs depend on sufficient insulin levels during a specific temporal window, when insulin receptor expression is highly upregulated. Furthermore, an insulin-enriched environment via nasal insulin application during the critical period facilitates OSNs regeneration even in non-diabetic mice. The present results have implications for intranasal application of insulin as potential clinical therapeutics to facilitate OSNs regeneration after the injury.

scholarly journals Aversive Learning Increases Release Probability of Olfactory Sensory Neurons

2019 ◽  
Author(s):  
Janardhan P. Bhattarai ◽  
Mary Schreck ◽  
Andrew H. Moberly ◽  
Wenqin Luo ◽  
Minghong Ma
Keyword(s):  
Sensory Neurons ◽  
Receptor Expression ◽  
Olfactory Sensory Neurons ◽  
Aversive Learning ◽  
Sensory Stimuli ◽  
Release Probability ◽  
Synaptic Release ◽  
Underlying Mechanisms ◽  
Peripheral Sensory ◽  
Cortical Influence

AbstractPredicting danger from previously associated sensory stimuli is essential for survival. Contributions from altered peripheral sensory inputs are implicated in this process, but the underlying mechanisms remain elusive. Here we use the mammalian olfactory system to investigate such mechanisms. Primary olfactory sensory neurons (OSNs) project their axons directly to the olfactory bulb (OB) glomeruli where their synaptic release is subject to local and cortical influence and neuromodulation. Pairing optogenetic activation of a single glomerulus with foot shock in mice induces freezing to the light stimulation alone during fear retrieval. This is accompanied by an increase in OSN release probability and a reduction in GABAB receptor expression in the conditioned glomerulus. Furthermore, freezing time is positively correlated with the release probability of OSNs in fear conditioned mice. These results suggest that aversive learning increases peripheral olfactory inputs at the first synapse, which may contribute to the behavioral outcome.

scholarly journals Deletion of the insulin receptor in sensory neurons increases pancreatic insulin levels

2018 ◽  
Vol 305 ◽  
pp. 97-107 ◽  
Author(s):  
Caleb W. Grote ◽  
Natalie M. Wilson ◽  
Natalie K. Katz ◽  
Brianne L. Guilford ◽  
Janelle M. Ryals ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Sensory Neurons ◽  
Insulin Levels ◽  
Pancreatic Insulin

scholarly journals Coordination of olfactory receptor choice with guidance receptor expression and function in olfactory sensory neurons

PLoS Genetics ◽  
2018 ◽  
Vol 14 (1) ◽  
pp. e1007164 ◽  
Author(s):  
Puneet Dang ◽  
Stephen A. Fisher ◽  
Derek J. Stefanik ◽  
Junhyong Kim ◽  
Jonathan A. Raper
Keyword(s):  
Sensory Neurons ◽  
Olfactory Receptor ◽  
Receptor Expression ◽  
Olfactory Sensory Neurons ◽  
And Function

scholarly journals Lhx2 Determines Odorant Receptor Expression Frequency in Mature Olfactory Sensory Neurons

eNeuro ◽  
2016 ◽  
Vol 3 (5) ◽  
pp. ENEURO.0230-16.2016 ◽  
Author(s):  
Guangfan Zhang ◽  
William B. Titlow ◽  
Stephanie M. Biecker ◽  
Arnold J. Stromberg ◽  
Timothy S. McClintock
Keyword(s):  
Sensory Neurons ◽  
Odorant Receptor ◽  
Receptor Expression ◽  
Olfactory Sensory Neurons ◽  
Expression Frequency

scholarly journals Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic

2019 ◽  
Author(s):  
Aashutosh Vihani ◽  
Xiaoyang Serene Hu ◽  
Sivaji Gundala ◽  
Sachiko Koyama ◽  
Eric Block ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Phenotypic Variability ◽  
Cell Types ◽  
Receptor Expression ◽  
Olfactory Sensory Neurons ◽  
Sexually Dimorphic ◽  
Main Olfactory Epithelium ◽  
Distinct Cell ◽  
Male Specific

AbstractUnderstanding how genes and experiences work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the context of the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell-types, in mice. We identified a subpopulation of at least three types of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated female mice and responded robustly to the male-specific semiochemicals 2-sec-butyl-4,5-dihydrothaizole and (methylthio)methanethiol. Sex-combined housing led to a robust attenuation of the female over-representation. Testing of Bax null mice revealed a Bax-dependence in generating the sexual dimorphism in sex-separated mice. Altogether, our results suggest a profound role of experience in influencing homeostatic neural lifespan mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.

scholarly journals Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aashutosh Vihani ◽  
Xiaoyang Serene Hu ◽  
Sivaji Gundala ◽  
Sachiko Koyama ◽  
Eric Block ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Olfactory Epithelium ◽  
Phenotypic Variability ◽  
Cell Types ◽  
Receptor Expression ◽  
Olfactory Sensory Neurons ◽  
Sexually Dimorphic ◽  
Sequencing Analysis ◽  
Main Olfactory Epithelium ◽  
Distinct Cell

Understanding how genes and experience work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell types in mice. We identified a subpopulation of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated mice and robustly responsive to sex-specific semiochemicals. Sex-combined housing led to an attenuation of the dimorphic representations. Single-cell sequencing analysis revealed an axis of activity-dependent gene expression amongst a subset of the dimorphic OSN populations. Finally, the pro-apoptotic gene Baxwas necessary to generate the dimorphic representations. Altogether, our results suggest a role of experience and activity in influencing homeostatic mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.

scholarly journals Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance

2015 ◽  
Vol 228 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Hamza Amine ◽  
Yacir Benomar ◽  
Adil Haimeur ◽  
Hafida Messaouri ◽  
Nadia Meskini ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
P38 Map Kinase ◽  
Receptor Expression ◽  
High Fat ◽  
Insulin Levels ◽  
Odontella Aurita ◽  
Plasma Insulin Levels

The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.

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