Nerve growth factor and its receptors TrkA and p75 are upregulated in the brain of mdx dystrophic mouse

B. Nico, D. Mangieri, A. De Luca, P. Corsi, V. Benagiano, R. Tamma, T. Annese, V. Longo, E. Crivellato, D. Ribatti

Research output: Contribution to journalArticle

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Abstract

Increased angiogenesis and an altered blood-brain barrier have been reported in the brain of dystrophin-deficient mdx mouse, an experimental model of Duchenne muscular dystrophy. To further elucidate the mechanisms underlying angiogenesis in Duchenne muscular dystrophy, in this study we evaluated whether nerve growth factor (NGF) and nerve growth factor receptors (NGFRs) are involved, then correlated NGF-NGFRs expression with vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) content and matrix metalloproteinases-2 and -9 (MMP-2 and -9) activity, by confocal laser microscopy and immunohistochemistry. Results showed that neurons, astrocytes and ependymal cells were strongly labeled by NGF in mdx brain, expressing NGFRs on glial and endothelial cells. In controls, NGF faintly labeled neurons and astrocytes, whereas endothelial cells were negative for NGFRs. Immunogold electron microscopy demonstrated NGFR gold particles on endothelial cells in mdx brain, while in controls few particles were recognizable only on glial end feet. Western blotting and real time polymerase chain reaction (RT-PCR) demonstrated a higher expression of NGF and NGFR mRNA and protein in mdx brain as compared to controls, and increase of VEGF-VEGFR-2 and active MMP-2 and -9 content. Overall, these data suggest that in the brain of mdx mice, an upregulation of the NGF-NGFRs system might be involved directly, or indirectly through the activation of VEGF-VEGFR-2 and MMP-2 and -9, in the angiogenic response taking place in this pathological condition.

Original languageEnglish
Pages (from-to)1057-1066
Number of pages10
JournalNeuroscience
Volume161
Issue number4
DOIs
Publication statusPublished - Jul 21 2009

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Inbred mdx Mouse
Nerve Growth Factor Receptors
Nerve Growth Factor
Brain
Matrix Metalloproteinases
Vascular Endothelial Growth Factor Receptor
Duchenne Muscular Dystrophy
Endothelial Cells
Confocal Microscopy
Neuroglia
Astrocytes
Vascular Endothelial Growth Factor A
Neurons
Vascular Endothelial Growth Factor Receptor-2
Dystrophin
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Blood-Brain Barrier
Gold
Real-Time Polymerase Chain Reaction

Keywords

  • angiogenesis
  • blood-brain barrier
  • mdx mouse
  • MMPs
  • NGF
  • VEGF

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nico, B., Mangieri, D., De Luca, A., Corsi, P., Benagiano, V., Tamma, R., ... Ribatti, D. (2009). Nerve growth factor and its receptors TrkA and p75 are upregulated in the brain of mdx dystrophic mouse. Neuroscience, 161(4), 1057-1066. https://doi.org/10.1016/j.neuroscience.2009.04.028

Nerve growth factor and its receptors TrkA and p75 are upregulated in the brain of mdx dystrophic mouse. / Nico, B.; Mangieri, D.; De Luca, A.; Corsi, P.; Benagiano, V.; Tamma, R.; Annese, T.; Longo, V.; Crivellato, E.; Ribatti, D.

In: Neuroscience, Vol. 161, No. 4, 21.07.2009, p. 1057-1066.

Research output: Contribution to journalArticle

Nico, B, Mangieri, D, De Luca, A, Corsi, P, Benagiano, V, Tamma, R, Annese, T, Longo, V, Crivellato, E & Ribatti, D 2009, 'Nerve growth factor and its receptors TrkA and p75 are upregulated in the brain of mdx dystrophic mouse', Neuroscience, vol. 161, no. 4, pp. 1057-1066. https://doi.org/10.1016/j.neuroscience.2009.04.028
Nico, B. ; Mangieri, D. ; De Luca, A. ; Corsi, P. ; Benagiano, V. ; Tamma, R. ; Annese, T. ; Longo, V. ; Crivellato, E. ; Ribatti, D. / Nerve growth factor and its receptors TrkA and p75 are upregulated in the brain of mdx dystrophic mouse. In: Neuroscience. 2009 ; Vol. 161, No. 4. pp. 1057-1066.
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AU - Mangieri, D.

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AU - Corsi, P.

AU - Benagiano, V.

AU - Tamma, R.

AU - Annese, T.

AU - Longo, V.

AU - Crivellato, E.

AU - Ribatti, D.

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