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Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia

BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature...

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Autores principales: Krishnasamy, Senthil, Weng, Yuan-Cheng, Thammisetty, Sai Sampath, Phaneuf, Daniel, Lalancette-Hebert, Melanie, Kriz, Jasna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335711/
https://www.ncbi.nlm.nih.gov/pubmed/28253906
http://dx.doi.org/10.1186/s12974-017-0816-7
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author Krishnasamy, Senthil
Weng, Yuan-Cheng
Thammisetty, Sai Sampath
Phaneuf, Daniel
Lalancette-Hebert, Melanie
Kriz, Jasna
author_facet Krishnasamy, Senthil
Weng, Yuan-Cheng
Thammisetty, Sai Sampath
Phaneuf, Daniel
Lalancette-Hebert, Melanie
Kriz, Jasna
author_sort Krishnasamy, Senthil
collection PubMed
description BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury. METHODS: To visualize effects of neuroinflammation on neurogenesis/gliogenesis, we created a transgenic model bearing the dual reporter system luciferase and GFP under transcriptional control of the murine nestin promoter. In this model, transcriptional activation of nestin was visualized from the brains of living animals using biophotonic/bioluminescence molecular imaging and a high resolution charged coupled device camera. Nestin induction profiles in vivo and in tissue sections were analyzed in two different experimental paradigms: middle cerebral artery occlusion and lipopolysaccharide-induced innate immune stimuli. RESULTS: We report here a context- and injury-dependent induction and cellular expression profile of nestin. While in the baseline conditions the nestin signal and/or GFP expression was restricted to neuronal progenitors, the cellular expression patterns of nestin following innate immune challenge and after stroke markedly differed shifting the cellular expression patterns towards activated microglia/macrophages and astrocytes. CONCLUSIONS: Our results suggest that nestin may serve as a context-dependent biomarker of inflammatory response in glial cells including activated microglia/macrophages. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-017-0816-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-53357112017-03-07 Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia Krishnasamy, Senthil Weng, Yuan-Cheng Thammisetty, Sai Sampath Phaneuf, Daniel Lalancette-Hebert, Melanie Kriz, Jasna J Neuroinflammation Research BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury. METHODS: To visualize effects of neuroinflammation on neurogenesis/gliogenesis, we created a transgenic model bearing the dual reporter system luciferase and GFP under transcriptional control of the murine nestin promoter. In this model, transcriptional activation of nestin was visualized from the brains of living animals using biophotonic/bioluminescence molecular imaging and a high resolution charged coupled device camera. Nestin induction profiles in vivo and in tissue sections were analyzed in two different experimental paradigms: middle cerebral artery occlusion and lipopolysaccharide-induced innate immune stimuli. RESULTS: We report here a context- and injury-dependent induction and cellular expression profile of nestin. While in the baseline conditions the nestin signal and/or GFP expression was restricted to neuronal progenitors, the cellular expression patterns of nestin following innate immune challenge and after stroke markedly differed shifting the cellular expression patterns towards activated microglia/macrophages and astrocytes. CONCLUSIONS: Our results suggest that nestin may serve as a context-dependent biomarker of inflammatory response in glial cells including activated microglia/macrophages. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-017-0816-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-03 /pmc/articles/PMC5335711/ /pubmed/28253906 http://dx.doi.org/10.1186/s12974-017-0816-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Krishnasamy, Senthil
Weng, Yuan-Cheng
Thammisetty, Sai Sampath
Phaneuf, Daniel
Lalancette-Hebert, Melanie
Kriz, Jasna
Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia
title Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia
title_full Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia
title_fullStr Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia
title_full_unstemmed Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia
title_short Molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia
title_sort molecular imaging of nestin in neuroinflammatory conditions reveals marked signal induction in activated microglia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335711/
https://www.ncbi.nlm.nih.gov/pubmed/28253906
http://dx.doi.org/10.1186/s12974-017-0816-7
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