title: FGF-2 is required to prevent astrogliosis in the facial nucleus after facial nerve injury and mechanical stimulation of denervated vibrissal muscles.
abstract: 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 intactFGF-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.
authors.affiliation: Department of Anatomy, Akdeniz University, Faculty of Medicine, Dumlupinar Bulvari 07058 Kampus, Antalya, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Hizay
authors.affiliation: Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, FR Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Seitz
authors.affiliation: Department of Oto-Rhino-Laryngology, University Hospital Cologne, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, FR Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Grosheva
authors.affiliation: Depeartment of Plastic-, Hand- and Reconstructive Microsurgery, Berlin, FR 12249, Germany.
authors.forename: Nektarios
authors.initials: N
authors.lastname: Sinis
authors.affiliation: Department of Anatomy, Akdeniz University, Faculty of Medicine, Dumlupinar Bulvari 07058 Kampus, Antalya, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Kaya
authors.affiliation: Department of Neurosurgery, Hospital Merheim, University of Witten-Herdecke, Ostmerheimer Straße 200, 51109 Cologne, Germany.
authors.forename: Habib
authors.initials: H
authors.lastname: Bendella
authors.affiliation: Department of Anatomy, Akdeniz University, Faculty of Medicine, Dumlupinar Bulvari 07058 Kampus, Antalya, Turkey.
authors.forename: Levent
authors.initials: L
authors.lastname: Sarikcioglu
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, University of Western Australia (M092) 35 Stirling Highway, CRAWLEY WA 6009, Australia.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Dunlop
authors.affiliation: Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50924 Cologne, FR Germany; angelov.anatomie@uni-koeln.de.
authors.forename: Doychin N
authors.initials: DN
authors.lastname: Angelov
keywords: FGF-2; astrogliosis; axotomy; facial nerve; polyinnervation; whisking function