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Cited by 146Multiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration MechanismsNerve injury and regeneration

Stimulation of the neurotrophin receptor TrkB on astrocytes drives nitric oxide production and neurodegeneration

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Colombo, Emanuela, Cordiglieri, Chiara, Melli, Giorgia, Newcombe, Jia, Krumbholz, Markus, Parada, Luis F., Medico, Enzo, Hohlfeld, Reinhard +2 more·2012·Journal of Experimental Medicine
DOI 10.1084/jem.20110698PMC PMC3302220
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Abstract

Neurotrophin growth factors support neuronal survival and function. In this study, we show that the expression of the neurotrophin receptor TrkB is induced on astrocytes in white matter lesions in multiple sclerosis (MS) patients and mice with experimental autoimmune encephalomyelitis (EAE). Surprisingly, mice lacking TrkB specifically in astrocytes were protected from EAE-induced neurodegeneration. In an in vitro assay, astrocytes stimulated with the TrkB agonist brain-derived neurotrophic factor (BDNF) released nitric oxide (NO), and conditioned medium from activated astrocytes had detrimental effects on the morphology and survival of neurons. This neurodegenerative process was amplified by NO produced by neurons. NO synthesis in the central nervous system during EAE depended on astrocyte TrkB. Together, these findings suggest that TrkB expression on astrocytes may represent a new target for neuroprotective therapies in MS.

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  • Neuronal damage due to nitrosative stress caused by astrocyte-derived nitric oxide occurs in multiple sclerosis.

    “An example is neuronal damage due to nitrosative stress caused by astrocyte-derived nitric oxide in MS33.”

    From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [33]

    The Results report nitrosylation in MS lesions, including affected axons near a TrkB-positive glial network. The Discussion establishes astrocyte-derived nitric oxide as a cause of neuronal damage in vitro, but says its contribution to neuronal damage in MS is speculative; it does not establish that causal chain in patients. Page numbers are not provided in our copy. (LLM, conf=0.88)

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References 60 · Cited by 146

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Authors
Colombo, E., Cordiglieri, C., Melli, G., Newcombe, J., Krumbholz, M., Parada, L. F., Medico, E., Hohlfeld, R., Meinl, E., & Farina, C.
Affiliations
  • IRCCS Ospedale San Raffaele (IT)
  • Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
  • UCL Queen Square Institute of Neurology (GB)
  • Max Planck Institute of Neurobiology (DE)
  • The University of Texas at Dallas (US)
  • Institute for Cancer Research and Treatment, 10060 Torino, Italy 8
Corresponding author
Farina, Cinthia
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2012-03-05
Volume
209
Issue
3
Pages
521-535
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20110698
PMC
PMC3302220
OpenAlex
W2110045140
Cited by
146
References
60
Citations by year
2026: 7 · 2025: 6 · 2024: 9 · 2023: 15 · 2022: 13 · 2021: 9 · 2020: 14 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 15 · 2013: 17 · 2012: 4
FWCI
10.61
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords
TrkB receptor, astrocytes, nitric oxide, neurodegeneration, multiple sclerosis, experimental autoimmune encephalomyelitis, brain-derived neurotrophic factor, neurotrophins, white matter lesions, neuroprotection, astrocyte-neuron interaction, neuronal survival
MeSH terms
Adult, Aged, Animals, Astrocytes, Cells, Cultured, Encephalomyelitis, Autoimmune, Experimental, Female, Humans, Mice, Inbred C57BL, Middle Aged, Multiple Sclerosis, Nerve Degeneration, Nitric Oxide, Up-Regulation, Case-Control Studies, Mice, Knockout, Brain-Derived Neurotrophic Factor, Receptor, Nerve Growth Factor, Receptor, trkB, Mice

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