Vol 74, No 4 (2015)
Original article
Published online: 2015-11-27

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Reduced level of synapsin I protein in the rat striatum after intraventricular administration of proteasome inhibitors: preliminary studies

S. Wójcik, J. H. Spodnik, J. Sidor-Kaczmarek, J. Moryś
DOI: 10.5603/FM.2015.0103
Pubmed: 26620501
Folia Morphol 2015;74(4):428-433.

Abstract

Background: We have recently described changes present in nigrostriatal terminals after intraperitoneal administration of MG-132 and changes that occur in the walls of the rat lateral ventricle after intraventricular administration of MG-132, lactacystin and epoxomicin — different classes of proteasome inhibitors. Substances that inhibit ubiquitin-proteasome system (UPS) activity, are intensively studied due to their potential role as novel therapeutic strategies in the treatment of cancer and ischaemia-reperfusion injury in the brain. The aim of this study is to determine the influence of intraventricular administration of MG-132, lactacystin and epoxomicin on the level in the rat striatum synapsin I — one of the most prominent neuron-specific phosphoproteins in the brain.

Materials and methods and Results: Two weeks after administration of studied proteasome inhibitors, substantial reduction (up to 80%) of synapsin I was ob­served in the rat striatum. Because neurons, and especially dopaminergic ones, are sensitive to the depletion of proteasome function, we assume that observed synapsin I decrease may reflect changes in population of striatal neurons and/or nigrostriatal terminals.

Conclusions: Understanding of cellular mechanisms standing behind our findings needs further studies, and could provide valuable contribution to the discussion on the mechanisms linking UPS inhibition and survival of neurons.