title: TIMP-1 abolishes MMP-9-dependent long-lasting long-term potentiation in the prefrontal cortex.
abstract: BACKGROUND
  Understanding of the molecular mechanisms of prefrontal cortex (PFC) plasticity is important for developing new treatment strategies for mental disorders such as depression and schizophrenia. Long-term potentiation (LTP) is a valid model for synaptic plasticity. The extracellular proteolytic system composed of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs) has recently been shown to play major role in the hippocampal plasticity.
  
  
  METHODS
  We tested whether induction of hippocampal-prefrontal LTP results in accumulation of tissue inhibitor of MMP-1, TIMP-1 mRNA, in the PFC of rats and whether adenovirally driven overexpression of TIMP-1 affects LTP. Additional study of slices was done with a specific MMP-9 inhibitor.
  
  
  RESULTS
  The TIMP-1 is induced in the rat medial PFC by stimuli evoking late LTP; its overexpression blocks the gelatinolytic activity of the MMP family; its overexpression before tetanization blocks late LTP in vivo; and MMP-9 inhibitor prevents late LTP in vitro.
  
  
  CONCLUSIONS
  We suggest a novel extracellular mechanism of late LTP in the PFC, engaging TIMP-1-controlled proteolysis as an element of information integration. Our results may also be meaningful to an understanding of mental diseases and development of new treatment strategies that are based on extracellular mechanisms of synaptic plasticity.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Nencki Institute, Warsaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Okulski
authors.forename: Therese M
authors.initials: TM
authors.lastname: Jay
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
authors.forename: Kamila
authors.initials: K
authors.lastname: Duniec
authors.forename: Joanna
authors.initials: J
authors.lastname: Dzwonek
authors.forename: Filip A
authors.initials: FA
authors.lastname: Konopacki
authors.forename: Grzegorz M
authors.initials: GM
authors.lastname: Wilczynski
authors.forename: Amelia
authors.initials: A
authors.lastname: Sánchez-Capelo
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
authors.forename: Leszek
authors.initials: L
authors.lastname: Kaczmarek
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000201:enzymology; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009434:Neural Pathways / Q000201:enzymology*; D017397:Prefrontal Cortex / Q000201:enzymology*; D011480:Protease Inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9