title: Differential molecular profiles of astrocytes in degeneration and re-innervation after sensory deafferentation of the adult rat cochlear nucleus.
abstract: Ablating the cochlea causes total sensory deafferentation of the cochlear nucleus. Over the first postoperative week, degeneration of the auditory nerve and its synaptic terminals in the cochlear nucleus temporally overlaps with its re-innervation by axon collaterals of medial olivocochlear neurons. At the same time, astrocytes increase in size and density. We investigated the time courses of the expression of ezrin, polysialic acid, matrix metalloprotease-9 and matrix metalloprotease-2 within these astrocytes during the first week following cochlear ablation. All four proteins are known to participate in degeneration, regeneration, or both, following injury of the central nervous system. In a next step, stereotaxic injections of kainic acid were made into the ventral nucleus of the trapezoid body prior to cochlear ablation to destroy the neurons that re-innervate the deafferented cochlear nucleus by axon collaterals developing growth-associated protein 43 immunoreactivity. This experimental design allowed us to distinguish between molecular processes associated with degeneration and those associated with re-innervation. Under these conditions, astrocytic growth and proliferation showed an unchanged deafferentation-induced pattern. Similarly, the distribution and amount of ezrin and matrix metalloprotease-9 in astrocytes after cochlear ablation developed in the same way as under cochlear ablation alone. In sharp contrast, the astrocytic expression of polysialic acid and matrix metalloprotease-2 normally invoked by cochlear ablation collapsed when re-innervation of the cochlear nucleus was inhibited by lesioning medial olivocochlear neurons with kainic acid. In conclusion, re-innervation, including axonal growth and synaptogenesis, seems to prompt astrocytes to recompose their molecular profile, paving the way for tissue reorganisation after nerve degeneration and loss of synaptic contacts.
authors.affiliation: Neurobiological Research Laboratory, Department of Otorhinolaryngology, University of Freiburg, Killianst 5, Freiburg 79106, Germany. robert.illing@uniklinik-freiburg.de
authors.forename: Michaela
authors.initials: M
authors.lastname: Fredrich
authors.forename: Anne C
authors.initials: AC
authors.lastname: Zeber
authors.forename: Heika
authors.initials: H
authors.lastname: Hildebrandt
authors.forename: Robert-Benjamin
authors.initials: RB
authors.lastname: Illing
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000502:physiology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation; D003051:Cochlea / Q000294:innervation; D003056:Cochlear Nerve / Q000166:cytology / Q000502:physiology; D017626:Cochlear Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003714:Denervation; D005260:Female; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012794:Sialic Acids / Q000378:metabolism; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D019922:GAP-43 Protein; D007608:Kainic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D012794:Sialic Acids; D000099149:Ezrin; C021319:polysialic acid; C522363:Mmp2 protein, rat; C572337:Mmp9 protein, rat
keywords: adult brain plasticity; cochlear ablation; degeneration; neuroplasticity; re-innervation