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

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, ou...

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Main Authors: Wiera, G, Wójtowicz, T, Lebida, K, Piotrowska, A, Drulis-Fajdasz, D, Gomułkiewicz, A, Gendosz, D, Podhorska-Okołów, M, Capogna, M, Wilczyński, G, Dzięgiel, P, Kaczmarek, L, Mozrzymas, J
Format: Journal article
Language:English
Published: 2012
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author Wiera, G
Wójtowicz, T
Lebida, K
Piotrowska, A
Drulis-Fajdasz, D
Gomułkiewicz, A
Gendosz, D
Podhorska-Okołów, M
Capogna, M
Wilczyński, G
Dzięgiel, P
Kaczmarek, L
Mozrzymas, J
author_facet Wiera, G
Wójtowicz, T
Lebida, K
Piotrowska, A
Drulis-Fajdasz, D
Gomułkiewicz, A
Gendosz, D
Podhorska-Okołów, M
Capogna, M
Wilczyński, G
Dzięgiel, P
Kaczmarek, L
Mozrzymas, J
author_sort Wiera, G
collection OXFORD
description 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.
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spelling oxford-uuid:8c4fdac6-8509-4644-8142-6c3f24f10d892022-03-26T22:43:47ZLong term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8c4fdac6-8509-4644-8142-6c3f24f10d89EnglishSymplectic Elements at Oxford2012Wiera, GWójtowicz, TLebida, KPiotrowska, ADrulis-Fajdasz, DGomułkiewicz, AGendosz, DPodhorska-Okołów, MCapogna, MWilczyński, GDzięgiel, PKaczmarek, LMozrzymas, JMatrix 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.
spellingShingle Wiera, G
Wójtowicz, T
Lebida, K
Piotrowska, A
Drulis-Fajdasz, D
Gomułkiewicz, A
Gendosz, D
Podhorska-Okołów, M
Capogna, M
Wilczyński, G
Dzięgiel, P
Kaczmarek, L
Mozrzymas, J
Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.
title Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.
title_full Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.
title_fullStr Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.
title_full_unstemmed Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.
title_short Long term potentiation affects intracellular metalloproteinases activity in the mossy fiber-CA3 pathway.
title_sort long term potentiation affects intracellular metalloproteinases activity in the mossy fiber ca3 pathway
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