Department of Neurotoxicology

Head:

Magdalena Zielinska, PhD - phone: (+48) 22 60 86 470;

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Secretary:

Dorota Rycko - (+48) 22 60 86 417; fax: (+48) 22 60 86 442

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Research staff

Prof. Jan Albrecht, PhD - phone: 22 60 86 617; This email address is being protected from spambots. You need JavaScript enabled to view it.

Magdalena Zielińska, PhD - phone: 22 60 86 470; This email address is being protected from spambots. You need JavaScript enabled to view it.

Monika Szeliga, PhD - phone: 22 60 86 416; This email address is being protected from spambots. You need JavaScript enabled to view it.

Marta Obara-Michlewska, PhD - phone: 22 60 86 416; This email address is being protected from spambots. You need JavaScript enabled to view it.

Anna Czarnecka, PhD - phone: 22 60 86 416; This email address is being protected from spambots. You need JavaScript enabled to view it.

Wojciech Hilgier, PhD - phone: 22 60 86 441; This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Ph.D. students

Ewelina Majewska, M.Sc., Ing. -  22 60 86 416; This email address is being protected from spambots. You need JavaScript enabled to view it. (KNOW)

Mariusz Popek, M.Sc., Ing. – 22 60 86 612, This email address is being protected from spambots. You need JavaScript enabled to view it. (KNOW)

Katarzyna Skowrońska, M.Sc. – 22 60 86 612, This email address is being protected from spambots. You need JavaScript enabled to view it. (Harmonia 4)

Katarzyna Dąbrowska, M.Sc., Ing - 22 60 86 416, This email address is being protected from spambots. You need JavaScript enabled to view it. (Hepentrans)

Krzysztof Milewski M.Sc. -  22 60 86 470, This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Technical staff

Małgorzata Bogacińska-Karaś, M.Sc. - 22 60 86 440; This email address is being protected from spambots. You need JavaScript enabled to view it.

Inez Fręśko - 22 60 86 421; This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Key research themes

  • Molecular and cellular mechanisms underlying hepatic encephalopathy (HE).
  • Astrocytic-neuronal-cerebral capillary endothelial cell  interaction in HE-induced brain  edema.
  • Roles of oxidative-nitrosative stress and ammonia- glutamine interplay.
  • Involvement of cGMP-associated intracellular signaling.
  • Glutamine and growth of malignant gliomas: roles of glutaminases.

 

Running projects funded

“ROLE OF ASTROCYTE GLUTAMINASE EXPRESSION BY INFLAMMATORY FACTORS IN HEPETIC ENCEPHALOPATHY.” Grant NCN Preludium no 2014/15/N/NZ5/03634, principal investigator: M.Sc. Krzysztof Milewski (2015 – 2017)

“CONTRIBUTION OF GLUTAMINE TRANSPORT TO BRAIN EDEMA AND DYSFUNCTION OF THE GLUTAMATERGIC SYNAPSE ASSOCIATED WITH HEPATIC ENCEPHALOPATHY.” Grant NCBR “CORE”  Pol-Nor/196190/26/2013, principal investigator: prof. Jan Albrecht (2013-2016)

“ROLE OF ASTROCYTIC NMDA RECEPTORS IN HYPERAMMONEMIC BRAIN EDEMA ACCOCIATED WITH HEPATIC ENCEPHALOPATHY.” Grant NCN Harmonia no 2013/08/M/NZ3/00869, principal investigator:  prof. Jan Albrecht (2013-2016)

“THE ROLE OF ASSYMETRIC DIMETHYLARGININE (ADMA) IN HEPATHIC ENCEPHALOPATHY: MARKER, MEDIATOR OR MODULATOR?” Grant NCN no 2013/09/B/NZ4/00536M, principal investigator dr Magdalena Zielińska (2014-2017)

“NEW 1,3,4-THIADIAZOLE DERIVATIVES AS INHIBITORS OF CRITICAL STEPS OF THE GLUTAMINE - GLUTAMATE CYCLE IN GLIOBLASTOMA  CELLS.” Grant NCN Sonata no 2013/11/D/NZ7/00925, principal investigator: dr Monika Szeliga (2014-2017)

“BLOOD-BRAIN BARIER IMPAIRMENT IN HEPATIC ENCEPHALOPATHY: ROLE OF MICRO RNA.” Grant NCN no DEC-2015/19/B/NZ4/01902, principal investigator: dr Magdalena Zielińska (2016-2019)

“CHANGES IN PROTEIN COMPOSITION AND ELECTROPHYSIOLOGICAL CHARACTERISTICS OF GLUTAMATERGIC SYNAPSE IN A MOUSE MODEL OF ACUTE HEPATIC ENCEPHALOPATHY: ROLE OF THE TRANSFORMING GROWTH FACTOR β1 (TGF β1).” Grant NCN Preludium No 2015/19/N/NZ5/02249, principal investigator: M.Sc. Ing. Mariusz Popek (2016-2019)

 

List of publications since 2012

• M. Skowrońska, J. Albrecht. Alterations of blood brain barrier function in hyperammonemia: An overview. Neurotox Res 2012;21:236-244. doi:10.1007/s12640-011-9269-4.

• W. Hilgier, J.W. Łazarewicz, L. Strużyńska, M.  Frontczak-Baniewicz, J. Albrecht. Repeated exposure of adult rats to Aroclor 1254 induces neuronal injury and impairs the neurochemical manifestations of the NMDA receptor-mediated intracellular signaling in the hippocampus. NeuroToxicology 2012;33:16-22.

• M. Skowrońska, M. Zielińska, J. Ruszkiewicz , D.Milatovic, L. Wójcik-Stanaszek M. Aschner, J. Albrecht. Ammonia increases paracellular permeability of rat brain endothelial cells by a mechanism encompassing oxidative/nitrosative stress and activation of matrix metalloproteinases. J Neurochem 2012;121:125-134. doi:10.1111/j.1471-4159.2012.07669.x

• M. Zielińska, M. Skowrońska, I.  Fręśko, J. Albrecht.  Upregulation of the heteromeric y(+)LAT2 transporter contributes to ammonia-induced increase of arginine uptake in rat cerebral cortical astrocytes. Neurochem Int 2012;61:531-535. doi:10.1016/j.neuint.2012.02.021.

• M. Juszczak, J. Matysiak, M. Szeliga, P. Pożarowski, A. Niewiadomy, J.  Albrecht, W. Rzeski. 2-Amino-1,3,4-thiadiazole derivative (FABT) inhibits the extracellular signal-regulated kinase pathway and induces cell cycle arrest in human non-small lung carcinoma cells. Bioorg Med Chem Lett 2012;22(17):5466-5469. doi:10.1016/j.bmcl.2012.07.036.

• M. Szeliga, A. Zgrzywa, M. Obara-Michlewska, J. Albrecht. Transfection of a human glioblastoma cell line with liver-type glutaminase (LGA) down-regulates the expression of DNA repair gene MGMT and sensitizes the cells to alkylating agents. J Neurochem 2012;23:428-436. doi:10.1111/j.1471-4159.2012.07917.x

• J. Ruszkiewicz, I. Fręśko, W. Hilgier, J. Albrecht. Decrease of glutathione content in the prefrontal cortical mitochondria of rats with acute hepatic encephalopathy: prevention by histidine. Metab Brain Dis 2013;28:11-14. doi:10.1007/s11011-012-9342-6.

• M. Skowrońska, J. Albrecht.  Oxidative and nitrosative stress in ammonia neurotoxicity. Neurochem Int 2013;62:731-737. doi:10.1016/j.neuint.2012.10.013.

• M. Obara-Michlewska , P. Tuszyńska , J. Albrecht. Ammonia upregulates kynurenine aminotransferase II mRNA expression in rat brain: a role for astrocytic NMDA receptors? Metab Brain Dis 2013;28:161-165. doi:10.1007/s11011-012-9353-3.

• M. Szeliga, M. Bogacińska-Karaś, A. Różycka, W. Hilgier, J. Marquez, J. Albrecht. Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the proliferation and viability of glioblastoma cells. Tumour Biol 2014;35:855-862. doi:10.1007/s13277-013-1247-4.

• M. Martín-Rufián, R. Nascimento-Gomes, A. Higuero, A.R. Crisma, J.A. Campos-Sandoval, M.C. Gómez-García, C. Cardona, T. Cheng,  C. Lobo, J.A. Segura, F.J Alonso, M. Szeliga, J.Albrecht, R. Curi, J. Márquez, A. Colquhoun, R.J. Deberardinis, J.M. Matés. Both GLS silencing and GLS2 overexpression synergize with oxidative stress against proliferation of glioma cells. J Mol Med (Berl) 2014;92:277-290. doi:10.1007/s00109-013-1105-2.

• M. Zielińska, M. Popek, J. Albrecht. Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: An emerging concept. Neurochem Res 2014;39:599-604. doi:10.1007/s11064-013-1141-x.

• W. Hilgier, T. Kocki, M. Obara-Michlewska, W.A. Turski, S.S. Oja, P. Saransaari, J. Albrecht. Modulation by kynurenine of extracellular kynurenate and glutamate in cerebral cortex of rats with acute liver failure. Pharmacol Rep 2014;66:466-470. doi:10.1016/j.pharep.2013.11.007.

• J. Albrecht , Ammonia. In: Aminoff M.J. and Daroff R.B. (eds.) Encyclopedia of the Neurological Sciences, 2nd edition. Oxford: Academic Press, 2014, vol. 1, pp. 148-151.

• M. Zielińska, M. Obara-Michlewska,W. Hilgier, J. Albrecht. Citrulline uptake in rat cerebral cortex slices: Modulation by thioacetamide-induced hepatic failure. Metab Brain Dis 2014;29(4):1053-60. doi:10.1007/s11011-013-9472-5.

• J. Albrecht, M. Zielińska. Deficit of astroglia-derived thrombospondin-1 and loss of synaptic proteins in hepatic encephalopathy: do ammonia-overexposed astrocytes derange the synaptic hardware? J Neurochem 2014;131(3):265-267. doi:10.1111/jnc.12823.

• J. Ruszkiewicz, J. Albrecht. Changes of the Thioredoxin System, Glutathione Peroxidase Activity and Total Antioxidant Capacity in Rat Brain Cortex During Acute Liver Failure: Modulation by L-histidine. Neurochem Res 2015 Feb;40(2):293-300. doi:10.1007/s11064-014-1417-9.

• M. Obara-Michlewska, J. Ruszkiewicz, M. Zielińska, A. Verkhratsky, J. Albrecht: Astroglial NMDA receptors inhibit expression of Kir4.1 channels in glutamate-overexposed astrocytes in vitro and in the brain of rats with acute liver failure. Neurochem Int 2015;88:20-25. doi:10.1016/j.neuint.2014.10.006.

• J. Ruszkiewicz, J. Albrecht. Changes in the mitochondrial antioxidant systems inneurodegenerative diseases and acute brain disorder. Neurochem Int 2015;88:66-72. doi:10.1016/j.neuint.2014.12.012.

• M. Szeliga, J. Albrecht. Opposing roles of glutaminase isoforms in determining glioblastoma cell phenotype. Neurochem Int 2015;88:6-9. doi:10.1016/j.neuint.2014.11.004.

• K. Milewski, W. Hilgier, J. Albrecht, M. Zielińska. The dimethylarginine (ADMA)/nitric oxide pathway in the brain and periphery of rats with thioacetamide-induced acute liver failure: Modulation by histidine. Neurochem Int 2015;88:26-31. doi:10.1016/j.neuint.2014.12.004.

• M. Szeliga, M.  Bogacińska-Karaś,  K. Kuźmicz, R. Rola, J. Albrecht .Downregulation of GLS2 in glioblastoma cells is related to DNA hypermethylation but not to the p53 status. Mol Carcinogen 2015 Aug 10. doi:10.1002/mc.22372 [Epub ahead of print].

• E. Zieminska, A. Stafiej, B. Toczylowska B, J. Albrecht, JW. Łazarewicz. Role of ryanodine and NMDA receptors in tetrabromobisphenol A-induced calcium imbalance and cytotoxicity in primary cultures of rat cerebellar granule cells. Neurotox Res 2015 Oct;28(3):195-208. doi:10.1007/s12640-015-9546-8.

• M. Zielińska, K. Dąbrowska, M.G. Hadera, U. Sonnewald, J. Albrecht. System N transporters are critical for glutamine release and modulate metabolic fluxes of glucose and acetate in cultured cortical astrocytes: changes induced by ammonia. J Neurochem 2016 Jan;136(2):329-38. doi:10.1111/jnc.13376.

• M. Zielińska, K. Milewski, M. Skowrońska, A. Gajos, E. Ziemińska, A. Beręsewicz, J. Albrecht . Induction of iNOS expression in ammonia-exposed cultured astrocytes is coupled to increased arginine transport by upregulated y+ LAT2 transporter. J Neurochem 2015 Dec;135(6):1272-1281. doi: 10.1111/jnc.13387.

• M. Szeliga, A. Różycka, P. Jędrak, S. Barańska, P. Janik, Z. Jamrozik, J. Albrecht. Expression of RNAs coding for metal transporters in blood of patients with Huntington's disease. Neurochem Res 2016 Feb;41(1-2):101-106. doi:10.1007/s11064-015-1737-4.

• M. Szeliga, J. Ćwikła, M. Obara-Michlewska, A. Cichocki, J. Albrecht.Glutaminases in slowly proliferating gastroenteropancreatic neuroendocrine neoplasms/tumors (GEP-NETs): Selective overexpression of mRNA coding for the KGA isoform. Exp Mol Pathol 2016 Feb;100(1):74-78. doi:10.1016/j.yexmp.2015.11.017.

• K. Milewski, M. Oria What we know: the inflammatory basis of hepatic encephalopathy. Metab Brain Dis 2015. doi:10.1007/s11011-015-9740-7 [Epub ahead of print].

• K. Milewski, W. Hilgier, I. Fręśko, R. Polowy, A. Podsiadłowska, E. Zołocińska, A.W. Grymanowska, R.K. Filipkowski, J. Albrecht, M. Zielińska. Carnosine reduces oxidative stress and reverses attenuation of righting and postural reflexes in rats with thioacetamide-induced liver failure. Neurochem Res 2016 Feb;41(1-2):376-84. doi:10.1007/s11064-015-1821-9.

• Jęśko H, Wilkaniec A, Cieślik M, Hilgier W, Gąssowska M, Lukiw WJ, Adamczyk A. Altered arginine metabolism in cells transfected with human wild-type beta amyloid precursor protein (βAPP). Curr Alzheimer Res 2016 Mar 14 [Epub ahead of print].