Fine - tuned MMP-9 level is critical for LTP maintenance in mossy fiber - CA3 hippocampal pathway

• Autorzy: Wiera G. , Wojtowicz T. , Chmielewska M. , Wawrzyniak M. , Kaczmarek L. , Dziegiel P. , Mozrzymas J.
• Języki publikacji: EN

Abstrakty

EN

Matrix metalloproteinases (MMPs) are a family of endopeptidases involved in degradation and turnover of extracellular matrix proteins. Among them, MMP-9 is implicated in learning and synaptic plasticity. We have shown using inhibitor FN-439 that MMPs play a critical role in LTP maintenance in the mossy fiber - CA3 hippocampal projection (Wójtowicz and Mozrzymas 2010). In the present study we address the specific role of MMP-9 in the plasticity of this pathway. Gel zymography revealed an up regulation of pro- and active form of MMP-9 in homogenates from slice fragments containing mf-CA3 projection, fixed 2 h after LTP induction. Interestingly, this effect was abolished when LTP was induced in the presence of protein synthesis inhibitor (cycloheximide). Moreover, the effects of cycloheximide and FN-439 on fEPSPs were indistinguishable for up to 2 h after LTP induction. Additionally, we observed on western blot a significant decrease in 30 kDa β-dystroglycan digestion product 2 hours after LTP induction. To further explore the mechanism of MMP-9 action, LTP was induced in slices from MMP-9-/- and MMP-9 overexpressing rodents. In slices from KO mice, the late phase of LTP was severely impaired, although not abolished (136% vs. 189% in WT). Surprisingly, in slices from MMP-9 overexpressing rats, LTP was impaired in a similar manner as in KO mice (113% vs. 171%). Moreover, in MMP-9 overexpressing rats, LTP induction was accompanied by increase in MMP-9 level (shown by gel zymography) similar to what was observed in WT rats. These results indicate that fine-tuned MMP-9 balance is critical for LTP consolidation in mf-CA3 pathway, as in the absence of MMP-9 or in conditions of its excess, LTP is impaired. These results may raise a possibility that impairment of optimal MMP-9 activity (implicated in schizophrenia or bipolar mood disorder) may be detrimental for cognitive processes. Supported by Ministry for Science and Higher Education grants PN/030/2006 and N N401 541540.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2011
• Tom: 71
• Numer: S
• Opis fizyczny: p.45

Twórcy

autor

Wiera G.

• Department of Molecular Animal Physiology, Wroclaw University, Wroclaw, Poland

autor

Wojtowicz T.

• Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

autor

Chmielewska M.

• Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland

autor

Wawrzyniak M.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology PAS, Warsaw, Poland

autor

Kaczmarek L.

• Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology PAS, Warsaw, Poland

autor

Dziegiel P.

• Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland

autor

Mozrzymas J.

• Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland

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