title: Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.
abstract: Matrix Metalloproteinases (MMPs) are a family of endopeptidases known to process extracellular proteins. In the last decade, studies carried out mainly on the Schaffer collateral-CA1 hippocampal projection have provided solid evidence that MMPs regulate synaptic plasticity and learning. Recently, our group has shown that MMP blockade disrupts LTP maintenance also in the mossy fiber-CA3 (mf-CA3) projection (Wojtowicz and Mozrzymas, 2010), where LTP mechanisms are profoundly different (NMDAR-independent and presynaptic expression site). However, how plasticity of this pathway correlates with activity and expression of MMPs remains unknown. Interestingly, several potential MMP substrates (especially of gelatinases) are localized intracellularly but little is known about MMP activity in this compartment. In the present study we have asked whether LTP is associated with the expression and activity of gelatinases in apparent intra- and extracellular compartments along mf-CA3 projection. In situ zymography showed that LTP induction was associated with increased gelatinases activity in the cytoplasm of the hilar and CA3 neurons. Using gelatin zymography, immunohistochemistry and immunofluorescent staining we found that this effect was due to de novo synthesis and activation of MMP-9 which, 2-3h after LTP induction was particularly evident in the cytoplasm. In contrast, MMP-2 was localized preferentially in the nuclei and was not affected by LTP induction. In conclusion, we demonstrate that LTP induction in the mf-CA3 pathway correlates with increased expression and activity of MMP-9 and provide the first evidence that this increase is particularly evident in the neuronal cytoplasm and nucleus.
authors.affiliation: Laboratory of Neuroscience, Department of Biophysics, Wroclaw Medical University, Chalubinskiego 3, 50-368, Wroclaw, Poland. gwiera@biol.uni.wroc.pl
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wiera
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wójtowicz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Lebida
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Piotrowska
authors.forename: Dominika
authors.initials: D
authors.lastname: Drulis-Fajdasz
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gomułkiewicz
authors.forename: Daria
authors.initials: D
authors.lastname: Gendosz
authors.forename: Marzena
authors.initials: M
authors.lastname: Podhorska-Okołów
authors.forename: Marco
authors.initials: M
authors.lastname: Capogna
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Wilczyński
authors.forename: Piotr
authors.initials: P
authors.lastname: Dzięgiel
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
authors.forename: Jerzy W
authors.initials: JW
authors.lastname: Mozrzymas
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000201:enzymology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D019599:Mossy Fibers, Hippocampal / Q000201:enzymology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9