Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway

作者：Wiera Grzegorz^*; Wojtowicz Tomasz; Lebida Katarzyna; Piotrowska Aleksandra; Drulis Fajdasz Dominika; Gomulkiewicz Agnieszka; Gendosz Dania; Podhorska Okolow Marzena; Capogna Marco; Wilczynski Grzegorz; Dziegiel Piotr; Kaczmarek Leszek; Mozrzymas Jerzy W

来源：Molecular and Cellular Neuroscience, 2012, 50(2): 147-159.

DOI：10.1016/j.mcn.2012.04.005

• LTP
• Metalloproteinase
• Mossy fiber
• Hippocampus
• Synaptic plasticity
• MMP-9

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 LIP maintenance also in the mossy fiber-CA3 (mf-CA3) projection (Wojtowicz and Mozrzymas. 2010), where LIP 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 LIP is associated with the expression and activity of gelatinases in apparent intra- and extracellular compartments along mf-CA3 projection. In situ zymography showed that LIP 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, 2-3 h after LIP induction was particularly evident in the cytoplasm. In contrast, MMP-2 was localized preferentially in the nuclei and was not affected by LIP induction. In conclusion, we demonstrate that LIP 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.

• 出版日期2012-6