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

Emanuela Colombo, Chiara Cordiglieri, Giorgia Melli, Jia Newcombe, Markus Krumbholz, Luis F. Parada, Enzo Medico, Reinhard Hohlfeld, Edgar Meinl, Cinthia Farina

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)521-535
Number of pages15
JournalJournal of Experimental Medicine
Volume209
Issue number3
DOIs
StatePublished - Mar 12 2012

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Nerve Growth Factor Receptors
Astrocytes
Nitric Oxide
Autoimmune Experimental Encephalomyelitis
Multiple Sclerosis
Neurons
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Conditioned Culture Medium
Intercellular Signaling Peptides and Proteins
Central Nervous System

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Colombo, E., Cordiglieri, C., Melli, G., Newcombe, J., Krumbholz, M., Parada, L. F., ... Farina, C. (2012). Stimulation of the neurotrophin receptor trkb on astrocytes drives nitric oxide production and neurodegeneration. Journal of Experimental Medicine, 209(3), 521-535. https://doi.org/10.1084/jem.20110698

Stimulation of the neurotrophin receptor trkb on astrocytes drives nitric oxide production and neurodegeneration. / Colombo, Emanuela; Cordiglieri, Chiara; Melli, Giorgia; Newcombe, Jia; Krumbholz, Markus; Parada, Luis F.; Medico, Enzo; Hohlfeld, Reinhard; Meinl, Edgar; Farina, Cinthia.

In: Journal of Experimental Medicine, Vol. 209, No. 3, 12.03.2012, p. 521-535.

Research output: Contribution to journalArticle

Colombo, E, Cordiglieri, C, Melli, G, Newcombe, J, Krumbholz, M, Parada, LF, Medico, E, Hohlfeld, R, Meinl, E & Farina, C 2012, 'Stimulation of the neurotrophin receptor trkb on astrocytes drives nitric oxide production and neurodegeneration', Journal of Experimental Medicine, vol. 209, no. 3, pp. 521-535. https://doi.org/10.1084/jem.20110698
Colombo, Emanuela ; Cordiglieri, Chiara ; Melli, Giorgia ; Newcombe, Jia ; Krumbholz, Markus ; Parada, Luis F. ; Medico, Enzo ; Hohlfeld, Reinhard ; Meinl, Edgar ; Farina, Cinthia. / Stimulation of the neurotrophin receptor trkb on astrocytes drives nitric oxide production and neurodegeneration. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 3. pp. 521-535.
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