FGF-2 is required to prevent astrogliosis in the facial nucleus after facial nerve injury and mechanical stimulation of denervated vibrissal muscles

A. Hizay, M. Seitz, M. Grosheva, N. Sinis, Y. Kaya, H. Bendella, L. Sarikcioglu, Sarah A. Dunlop, D.N. Angelov

    Research output: Contribution to journalArticle

    4 Citations (Scopus)

    Abstract

    © 2016 by the Journal of Biomedical Research. All rights reserved.Recently, we have shown that manual stimulation of paralyzed vibrissal muscles after facial-facial anastomosis reduced the poly-innervation of neuromuscular junctions and restored vibrissal whisking. Using gene knock outs, we found a differential dependence of manual stimulation effects on growth factors. Thus, insulin-like growth factor- 1 and brain-derived neurotrophic factor are required to underpin manual stimulation-mediated improvements, whereas FGF-2 is not. The lack of dependence on FGF-2 in mediating these peripheral effects prompted us to look centrally, i.e. within the facial nucleus where increased astrogliosis after facial-facial anastomosis follows "synaptic stripping". We measured the intensity of Cy3-fluorescence after immunostaining for glial fibrillary acidic protein (GFAP) as an indirect indicator of synaptic coverage of axotomized neurons in the facial nucleus of mice lacking FGF-2 (FGF-2-/- mice). There was no difference in GFAP-Cy3-fluorescence (pixel number, gray value range 17-103) between intact wildtype mice (2.12± 0.37×107) and their intact FGF-2-/- counterparts (2.12±0.27×107) nor after facial-facial anastomosis +handling (wildtype: 4.06±0.32×107; FGF-2-/-: 4.39±0.17×107). However, after facial- facial anastomosis, GFAP-Cy3-fluorescence remained elevated in FGF-2-/--animals (4.54±0.12×107), whereas manual stimulation reduced the intensity of GFAP-immunofluorescence in wild type mice to values that were not significantly different from intact mice (2.63±0.39×10 ). We conclude that FGF-2 is not required to underpin the beneficial effects of manual stimulation at the neuro-muscular junction, but it is required to minimize astrogliosis in the brainstem and, by implication, restore synaptic coverage of recovering facial motoneurons.
    Original languageEnglish
    Pages (from-to)142-148
    Number of pages7
    JournalJournal of Biomedical Research
    Volume30
    Issue number2
    DOIs
    Publication statusPublished - 2016

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