title: The extracellular matrix glycoprotein tenascin-C and matrix metalloproteinases modify cerebellar structural plasticity by exposure to an enriched environment.
abstract: The importance of the extracellular matrix (ECM) glycoprotein tenascin-C (TnC) and the ECM degrading enzymes, matrix metalloproteinases (MMPs) -2 and -9, in cerebellar histogenesis is well established. This study aimed to examine whether there is a functional relationship between these molecules in regulating structural plasticity of the lateral deep cerebellar nucleus. To this end, starting from postnatal day 21, TnC- or MMP-9-deficient mice were exposed to an enriched environment (EE). We show that 8 weeks of exposure to EE leads to reduced lectin-based staining of perineuronal nets (PNNs), reduction in the size of GABAergic and increase in the number and size of glutamatergic synaptic terminals in wild-type mice. Conversely, TnC-deficient mice showed reduced staining of PNNs compared to wild-type mice maintained under standard conditions, and exposure to EE did not further reduce, but even slightly increased PNN staining. EE did not affect the densities of the two types of synaptic terminals in TnC-deficient mice, while the size of inhibitory, but not excitatory synaptic terminals was increased. In the time frame of 4-8 weeks, MMP-9, but not MMP-2, was observed to influence PNN remodeling and cerebellar synaptic plasticity as revealed by measurement of MMP-9 activity and colocalization with PNNs and synaptic markers. These findings were supported by observations on MMP-9-deficient mice. The present study suggests that TnC contributes to the regulation of structural plasticity in the cerebellum and that interactions between TnC and MMP-9 are likely to be important for these processes to occur.
authors.affiliation: Center for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000, Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Stamenkovic
authors.affiliation: Center for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000, Belgrade, Serbia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamenkovic
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jaworski
authors.affiliation: Laboratory of Physiology and Pathophysiology, Center for Preclinical Research and Technology, The Medical University of Warsaw, 02-097, Warsaw, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Gawlak
authors.affiliation: Center for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000, Belgrade, Serbia.
authors.forename: Milos
authors.initials: M
authors.lastname: Jovanovic
authors.affiliation: Experimental Neurophysiology, University Hospital Cologne, 50931, Cologne, Germany.|Experimental Neurophysiology, German Center for Neurodegenerative Diseases, 53175, Bonn, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovcevski
authors.affiliation: Laboratory of Neuromorphology, Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland.
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Wilczynski
authors.affiliation: Laboratory of Neurobiology, Nencki Institute of Experimental Biology, 02-093, Warsaw, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.affiliation: Department of Cell Biology and Neuroscience, W. M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ, 08854, USA.|Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong, 515041, People's Republic of China.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.affiliation: Center for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000, Belgrade, Serbia.
authors.forename: Lidija
authors.initials: L
authors.lastname: Radenovic
authors.affiliation: Center for Laser Microscopy, Department of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, 11000, Belgrade, Serbia. pandjus@bio.bg.ac.rs.
authors.forename: Pavle R
authors.initials: PR
authors.lastname: Andjus
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism / Q000502:physiology*; D004777:Environment; D018093:Gelatinases / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D019063:Tenascin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D019063:Tenascin; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Cerebellum; Enriched environment; Matrix metalloproteinases-2 and -9; Perineuronal net; Synaptic plasticity; Tenascin-C