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2015 | 74 | 4 |
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Reduced level of synapsin I protein in the rat striatum after intraventricular administration of proteasome inhibitors: preliminary studies

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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. (Folia Morphol 2015; 74, 4: 428–433)
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  • Department of Anatomy and Neurobiology, Medical University of Gdansk, Gdansk, Poland
  • Department of Anatomy and Neurobiology, Medical University of Gdansk, Gdansk, Poland
  • Department of Anatomy and Neurobiology, Medical University of Gdansk, Gdansk, Poland
  • Department of Anatomy and Neurobiology, Medical University of Gdansk, Gdansk, Poland
  • 1. Badowska-Szalewska E, Ludkiewicz B, Sidor-Kaczmarek J, Lietzau G, Spodnik JH, Swietlik D, Domaradzka-Pytel B, Morys J (2013) Hippocampal interleukin-1beta in the juvenile and middle-aged rat: response to chronic forced swim or high-light open-field stress stimulation. Acta Neurobiol Exp, 73: 364–378. doi:7326 [pii].
  • 2. Bedford L, Hay D, Devoy A, Paine S, Powe DG, Seth R, Gray T, Topham I, Fone K, Rezvani N, Mee M, Soane T, Layfield R, Sheppard PW, Ebendal T, Usoskin D, Lowe J, Mayer RJ (2008) Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies. J Neurosci, 28: 8189–8198. doi: 10.1523/JNEUROSCI.2218-08.2008.
  • 3. Brener O, Dunkelmann T, Gremer L, van Groen T, Mirecka EA, Kadish I, Willuweit A, Kutzsche J, Jurgens D, Rudolph S, Tusche M, Bongen P,Pietruszka J, Oesterhelt F, Langen KJ, Demuth HU, Janssen A, Hoyer W, Funke SA, Nagel-Steger L, Willbold D (2015) QIAD assay for quantitating a compound’s efficacy in elimination of toxic Abeta oligomers. Sci Rep, 5: 13222. doi: 10.1038/srep13222.
  • 4. Ding Q, Dimayuga E, Martin S, Bruce-Keller AJ, Nukala V, Cuervo AM, Keller JN (2003) Characterization of chronic low-level proteasome inhibition on neural homeostasis. J Neurochem, 86: 489–497.
  • 5. Dredge BK, Jensen KB (2011) NeuN/Rbfox3 nuclear and cytoplasmic isoforms differentially regulate alternative splicing and nonsense-mediated decay of Rbfox2. PLoS One, 6: e21585. doi: 10.1371/journal.pone.0021585.
  • 6. Fioravante D, Liu RY, Byrne JH (2008) The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia. J Neurosci, 28: 10245–10256. doi: 10.1523/JNEUROSCI.2139-08.2008.
  • 7. Gelman BB, Nguyen TP (2010) Synaptic proteins linked to HIV-1 infection and immunoproteasome induction: proteomic analysis of human synaptosomes. J Neuroimmune Pharmacol, 5: 92–102. doi: 10.1007/s11481-009-9168-0.
  • 8. Greengard P, Valtorta F, Czernik AJ, Benfenati F (1993) Synaptic vesicle phosphoproteins and regulation of synaptic function. Science, 259: 780–785.
  • 9. Hamano T, Gendron TF, Ko LW, Yen SH (2009) Concentration-dependent effects of proteasomal inhibition on tau processing in a cellular model of tauopathy. Int J Clin Exp Pathol, 2: 561–573.
  • 10. Ho L, Guo Y, Spielman L, Petrescu O, Haroutunian V, Purohit D, Czernik A, Yemul S, Aisen PS, Mohs R, Pasinetti GM (2001) Altered expression of a-type but not b-type synapsin isoform in the brain of patients at high risk for Alzheimer’s disease assessed by DNA microarray technique. Neurosci Lett, 298:191–194.
  • 11. Jang BG, In S, Choi B, Kim MJ (2014) Beta-amyloid oligomers induce early loss of presynaptic proteins in primary neurons by caspase-dependent and proteasomedependent mechanisms. Neuroreport, 25: 1281–1288. doi: 10.1097/WNR.0000000000000260.
  • 12. Kandilis AN, Karidis NP, Kouraklis G, Patsouris E, Vasileiou I, Theocharis S (2014) Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury? Expert Opin Investig Drugs, 23: 67–80. doi:10.1517/13543 784.2013.840287.
  • 13. Kim KK, Adelstein RS, Kawamoto S (2009) Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors. J Biol Chem, 284: 31052–31061. doi: 10.1074/jbc.M109.052969.
  • 14. Lazarevic V, Schone C, Heine M, Gundelfinger ED, Fejtova A (2011) Extensive remodeling of the presynaptic cytomatrix upon homeostatic adaptation to network activity silencing. J Neurosci, 31: 10189–10200. doi: 10.1523/JNEUROSCI.2088-11.2011.
  • 15. Lorenc-Koci E, Lenda T, Antkiewicz-Michaluk L, Wardas J, Domin H, Smialowska M, Konieczny J (2011) Different effects of intranigral and intrastriatal administration of the proteasome inhibitor lactacystin on typical neurochemical and histological markers of Parkinson’s disease in rats. Neurochem Int, 58: 839–849. doi: 10.1016/j.neuint.2011.03.013.
  • 16. Maxeiner S, Glassmann A, Kao HT, Schilling K (2014) The molecular basis of the specificity and cross-reactivity of the NeuN epitope of the neuron-specific splicing regulator, Rbfox3. Histochem Cell Biol, 141: 43–55. doi:10.1007/s00418-013-1159-9.
  • 17. Miwa H, Kubo T, Suzuki A, Nishi K, Kondo T (2005) Retrograde dopaminergic neuron degeneration following intrastriatal proteasome inhibition. Neurosci Lett, 380: 93–98. doi: 10.1016/j.neulet.2005.01.024.
  • 18. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development, 116: 201–211.
  • 19. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates edn. 4th Ed. Academic, San Diego, London.
  • 20. Qin S, Hu XY, Xu H, Zhou JN (2004) Regional alteration of synapsin I in the hippocampal formation of Alzheimer’s disease patients. Acta Neuropathol, 107: 209–215. doi: 10.1007/s00401-003-0800-4.
  • 21. Raghavendra Rao VL, Bowen KK, Dhodda VK, Song G, Franklin JL, Gavva NR, Dempsey RJ (2002) Gene expression analysis of spontaneously hypertensive rat cerebral cortex following transient focal cerebral ischemia. J Neurochem, 83: 1072–1086.
  • 22. Rogers N, Paine S, Bedford L, Layfield R (2010) Review: the ubiquitin-proteasome system: contributions to cell death or survival in neurodegeneration. Neuropathol Appl Neurobiol, 36: 113–124. doi: 10.1111/j.1365-2990.2010.01063.x.
  • 23. Szabo Z, Ying Z, Radak Z, Gomez-Pinilla F (2010) Voluntary exercise may engage proteasome function to benefit the brain after trauma. Brain Res, 1341: 25–31. doi: 10.1016/j.brainres.2009.01.035.
  • 24. Valtorta F, Pozzi D, Benfenati F, Fornasiero EF (2011) The synapsins: multitask modulators of neuronal development. Semin Cell Dev Biol, 22: 378–386. doi: 10.1016/j.semcdb.2011.07.008.
  • 25. Villamar-Cruz O, Manjarrez-Marmolejo J, Alvarado R, Camacho-Arroyo I (2006) Regulation of the content of progesterone and estrogen receptors, and their cofactors SRC-1 and SMRT by the 26S proteasome in the rat brain during the estrous cycle. Brain Res Bull, 69: 276–281. doi: 10.1016/j.brainresbull.2005.12.006.
  • 26. Wojcik S (2013) Crosstalk between autophagy and proteasome protein degradation systems: possible implications for cancer therapy. Folia Histochem Cytobiol, 51: 249–264. doi: 10.5603/FHC.2013.0036.
  • 27. Wojcik S, Spodnik JH, Dziewiatkowski J, Spodnik E, Morys J (2015) Morphological changes within the rat lateral ventricle after the administration of proteasome inhibitors. PLoS One, 2015; 10: e0140536. doi: 10.1371/journal.pone.0140536. eCollection 2015.
  • 28. Wojcik S, Spodnik JH, Spodnik E, Dziewiatkowski J, Morys J (2014) Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132. Folia Neuropathol, 52: 41–55.
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