title: Inhibition of MMP-2 but not MMP-9 influences inner ear spiral ganglion neurons in vitro.
abstract: Matrix metalloproteinases (MMPs) play an important role in modeling of the extracellular matrix. There is increasing evidence that these proteases are important in neurite elongation and axonal guidance during development in the central nervous system and retina. Moreover, they are also expressed after acute injury and can be the key mediators of pathogenesis. However, the role of MMPs in the inner ear is largely unknown. Our group recently demonstrated that general inhibition of MMPs resulted in auditory hair cell loss in vitro. In the present study, we investigated the role of MMPs in inner ear spiral ganglion neuron (SGN) survival, neuritogenesis and neurite extension by blocking MMPs known to be involved in axonal guidance, neurite elongation, and apoptosis in other neuronal systems. Spiral ganglion (SG) explants from 5-day-old Wistar rats were treated with different concentrations of the general MMP inhibitor GM6001, a specific MMP-2 inhibitor, and a specific MMP-9 inhibitor, in vitro. The general inhibitor of MMPs and the specific inhibition of MMP-2 significantly reduced both the number of neurites that extended from SG explants, as well as the length of individual neurites. However, neither the general inhibitor of MMPs nor the specific inhibition of MMP-2 influenced SGN survival. Inhibition of MMP-9 had no influence on SGNs. The data suggest that MMPs, and more specifically MMP-2, influence the growth of developing afferent neurites in the mammalian inner ear in vivo.
authors.affiliation: Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Sung
authors.forename: Eric
authors.initials: E
authors.lastname: Wei
authors.forename: Eduardo
authors.initials: E
authors.lastname: Chavez
authors.forename: Neha
authors.initials: N
authors.lastname: Jain
authors.forename: Soledad
authors.initials: S
authors.lastname: Levano
authors.forename: Laura
authors.initials: L
authors.lastname: Binkert
authors.forename: Alessia
authors.initials: A
authors.lastname: Ramseier
authors.forename: Cristian
authors.initials: C
authors.lastname: Setz
authors.forename: Daniel
authors.initials: D
authors.lastname: Bodmer
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
authors.forename: Yves
authors.initials: Y
authors.lastname: Brand
mesh_terms: D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D007758:Ear, Inner / Q000166:cytology*; D007760:Labyrinth Supporting Cells / Q000166:cytology / Q000201:enzymology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D013136:Spiral Ganglion / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9