Cargando…
Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor
Apart from its pivotal role in the regulation of carbohydrate metabolism, insulin exerts important neurotrophic and neuromodulator effects on dorsal root ganglion (DRG) neurons. The neurite outgrowth-promoting effect is one of the salient features of insulin’s action on cultured DRG neurons. Althoug...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191510/ https://www.ncbi.nlm.nih.gov/pubmed/30364236 http://dx.doi.org/10.3389/fnins.2018.00732 |
_version_ | 1783363731236847616 |
---|---|
author | Lázár, Bence András Jancsó, Gábor Pálvölgyi, Laura Dobos, Ildikó Nagy, István Sántha, Péter |
author_facet | Lázár, Bence András Jancsó, Gábor Pálvölgyi, Laura Dobos, Ildikó Nagy, István Sántha, Péter |
author_sort | Lázár, Bence András |
collection | PubMed |
description | Apart from its pivotal role in the regulation of carbohydrate metabolism, insulin exerts important neurotrophic and neuromodulator effects on dorsal root ganglion (DRG) neurons. The neurite outgrowth-promoting effect is one of the salient features of insulin’s action on cultured DRG neurons. Although it has been established that a significant population of DRG neurons express the insulin receptor (InsR), the significance of InsR expression and the chemical phenotype of DRG neurons in relation to the neurite outgrowth-promoting effect of insulin has not been studied. Therefore, in this study by using immunohistochemical and quantitative stereological methods we evaluated the effect of insulin on neurite outgrowth of DRG neurons of different chemical phenotypes which express or lack the InsR. Insulin, at a concentration of 10 nM, significantly increased total neurite length, the length of the longest neurite and the number of branch points of cultured DRG neurons as compared to neurons cultured in control medium or in the presence of 1 μM insulin. In both the control and the insulin exposed cultures, ∼43% of neurons displayed InsR-immunoreactivity. The proportions of transient receptor potential vanilloid type 1 receptor (TRPV1)-immunoreactive (IR), calcitonin gene-related peptide (CGRP)-IR and Bandeiraea simplicifolia isolectin B4 (IB4)-binding neurons amounted to ∼61%, ∼57%, and ∼31% of DRG neurons IR for the InsR. Of the IB4-positive population only neurons expressing the InsR were responsive to insulin. In contrast, TRPV1-IR nociceptive and CGRP-IR peptidergic neurons showed increased tendency for neurite outgrowth which was further enhanced by insulin. However, the responsiveness of DRG neurons expressing the InsR was superior to populations of DRG neurons which lack this receptor. The findings also revealed that besides the expression of the InsR, inherent properties of peptidergic, but not non-peptidergic nociceptive neurons may also significantly contribute to the mechanisms of neurite outgrowth of DRG neurons. These observations suggest distinct regenerative propensity for differing populations of DRG neurons which is significantly affected through insulin receptor signaling. |
format | Online Article Text |
id | pubmed-6191510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61915102018-10-24 Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor Lázár, Bence András Jancsó, Gábor Pálvölgyi, Laura Dobos, Ildikó Nagy, István Sántha, Péter Front Neurosci Neuroscience Apart from its pivotal role in the regulation of carbohydrate metabolism, insulin exerts important neurotrophic and neuromodulator effects on dorsal root ganglion (DRG) neurons. The neurite outgrowth-promoting effect is one of the salient features of insulin’s action on cultured DRG neurons. Although it has been established that a significant population of DRG neurons express the insulin receptor (InsR), the significance of InsR expression and the chemical phenotype of DRG neurons in relation to the neurite outgrowth-promoting effect of insulin has not been studied. Therefore, in this study by using immunohistochemical and quantitative stereological methods we evaluated the effect of insulin on neurite outgrowth of DRG neurons of different chemical phenotypes which express or lack the InsR. Insulin, at a concentration of 10 nM, significantly increased total neurite length, the length of the longest neurite and the number of branch points of cultured DRG neurons as compared to neurons cultured in control medium or in the presence of 1 μM insulin. In both the control and the insulin exposed cultures, ∼43% of neurons displayed InsR-immunoreactivity. The proportions of transient receptor potential vanilloid type 1 receptor (TRPV1)-immunoreactive (IR), calcitonin gene-related peptide (CGRP)-IR and Bandeiraea simplicifolia isolectin B4 (IB4)-binding neurons amounted to ∼61%, ∼57%, and ∼31% of DRG neurons IR for the InsR. Of the IB4-positive population only neurons expressing the InsR were responsive to insulin. In contrast, TRPV1-IR nociceptive and CGRP-IR peptidergic neurons showed increased tendency for neurite outgrowth which was further enhanced by insulin. However, the responsiveness of DRG neurons expressing the InsR was superior to populations of DRG neurons which lack this receptor. The findings also revealed that besides the expression of the InsR, inherent properties of peptidergic, but not non-peptidergic nociceptive neurons may also significantly contribute to the mechanisms of neurite outgrowth of DRG neurons. These observations suggest distinct regenerative propensity for differing populations of DRG neurons which is significantly affected through insulin receptor signaling. Frontiers Media S.A. 2018-10-10 /pmc/articles/PMC6191510/ /pubmed/30364236 http://dx.doi.org/10.3389/fnins.2018.00732 Text en Copyright © 2018 Lázár, Jancsó, Pálvölgyi, Dobos, Nagy and Sántha. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Lázár, Bence András Jancsó, Gábor Pálvölgyi, Laura Dobos, Ildikó Nagy, István Sántha, Péter Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor |
title | Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor |
title_full | Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor |
title_fullStr | Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor |
title_full_unstemmed | Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor |
title_short | Insulin Confers Differing Effects on Neurite Outgrowth in Separate Populations of Cultured Dorsal Root Ganglion Neurons: The Role of the Insulin Receptor |
title_sort | insulin confers differing effects on neurite outgrowth in separate populations of cultured dorsal root ganglion neurons: the role of the insulin receptor |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191510/ https://www.ncbi.nlm.nih.gov/pubmed/30364236 http://dx.doi.org/10.3389/fnins.2018.00732 |
work_keys_str_mv | AT lazarbenceandras insulinconfersdifferingeffectsonneuriteoutgrowthinseparatepopulationsofcultureddorsalrootganglionneuronstheroleoftheinsulinreceptor AT jancsogabor insulinconfersdifferingeffectsonneuriteoutgrowthinseparatepopulationsofcultureddorsalrootganglionneuronstheroleoftheinsulinreceptor AT palvolgyilaura insulinconfersdifferingeffectsonneuriteoutgrowthinseparatepopulationsofcultureddorsalrootganglionneuronstheroleoftheinsulinreceptor AT dobosildiko insulinconfersdifferingeffectsonneuriteoutgrowthinseparatepopulationsofcultureddorsalrootganglionneuronstheroleoftheinsulinreceptor AT nagyistvan insulinconfersdifferingeffectsonneuriteoutgrowthinseparatepopulationsofcultureddorsalrootganglionneuronstheroleoftheinsulinreceptor AT santhapeter insulinconfersdifferingeffectsonneuriteoutgrowthinseparatepopulationsofcultureddorsalrootganglionneuronstheroleoftheinsulinreceptor |