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.

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.

Krzysztof Milewski PhD -  22 60 86 470, 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)

Karolina Orzeł , M.Sc., Ing., This email address is being protected from spambots. You need JavaScript enabled to view it.

Marek Pawlik, , M.Sc., Ing. , 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

"Proteinkinase B signalling pathway in glioblastoma cells transfected with sequence encoding liver-type glutaminase (GAB)" grant NCN Preludium12 no 2016/23/N/NZ5/01428, principal investigator M.sc. Ing. Ewelina Majewska (2017-2019)

“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)

"Role of glutamine synthesis in the initial phase of temporal lobe epilepsy in the juvenile rat lithium-pilocarpine model: mechanism of activation of glutamine synthetase. " Grant NCN OPUS No 2016/23/13/NZ4/03678, principal investigator prof. Jan Albrecht (2017-2020)

”Farnesyl X receptor in the brain - a new element in the pathomechanism of acute hepatic encephalopathy” Grant NCN Miniatura 1 No. 2017/01/X/NZ4/00110, principal investigator dr Anna Czarnecka (2017-2018)

 

List of publications since 2012

  • Popek M, Bobula B, Sowa J, Hess G, Polowy R, Filipkowski RK, Frontczak-Baniewicz M, Zabłocka B, Albrecht J, Zielińska M: Cortical Synaptic Transmission and Plasticity in Acute Liver Failure Are Decreased by Presynaptic Events. Mol Neurobiol. 2017 Jan 23. doi: 10.1007/s12035-016-0367-4. [Epub ahead of print]
  • Milewski K, Bogacińska-Karaś M, Fręśko I, Hilgier W, Jaźwiec R, Albrecht J, Zielińska M: Ammonia Reduces Intracellular Asymmetric Dimethylarginine in Cultured Astrocytes Stimulating Its y⁺LAT2 Carrier-Mediated Loss. Int J Mol Sci. 2017 Nov 2;18(11). pii: E2308. doi: 10.3390/ijms18112308.
  • Majewska E, Rola R, Barczewska M, Marquez J, Albrecht J, Szeliga M: Transcription factor GATA3 expression is induced by GLS2 overexpression in a glioblastoma cell line but is GLS2-independent in patient-derived glioblastoma. J Physiol Pharmacol. 2017 Apr;68(2):209-214.
  • Magdalena Zielińska and Michael Aschner Enthusiasm scientifically oriented: the Preface  for the Special Issue Dedicated to Jan Albrecht. Neurochem Res. 2017 Mar;42(3):711-712. doi: 10.1007/s11064-016-2164-x.
  • Czarnecka A, Milewski K, Zielińska M.Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or Association? Neurochem Res. 2017 Mar;42(3):750-761. doi: 10.1007/s11064-016-2111-x.
  • Ewelina Majewska, Monika Szeliga. AKT/GSK3β Signaling in Glioblastoma. Neurochem Res. 2017 Mar;42(3):918-924. doi: 10.1007/s11064-016-2044-4.
  • Czarnecka A, Milewski K, Jaźwiec R, Zielińska M: Intracerebral Administration of S-Adenosylhomocysteine or S-Adenosylmethionine Attenuates the Increases in the Cortical Extracellular Levels of Dimethylarginines Without Affecting cGMP Level in Rats with Acute Liver Failure. Neurotox Res. 2017 Jan;31(1):99-108. doi: 10.1007/s12640-016-9668-7.
  • Zielińska M, Dąbrowska K, Hadera MG, Sonnewald U, Albrecht J; 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 136:2, 329–338.
  • Milewski K, Hilgier W, Fręśko I, Polowy R, Podsiadłowska A, Zołocińska E, Grymanowska AW, Filipkowski RK, Albrecht J, Zielińska M: 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.
  • Szeliga M, Ćwikła J, Obara-Michlewska M, Cichocki A, Albrecht J. 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):74-8. doi: 10.1016/j.yexmp.2015.11.017.
  • Szeliga M, Różycka A, Jędrak P, Barańska S, Janik P, Jamrozik Z, Albrecht J. Expression of RNAs Coding for Metal Transporters in Blood of Patients with Huntington's Disease. Neurochem Res. 2016 Feb;41(1-2):101-6. doi: 10.1007/s11064-015-1737-4.
  • Szeliga M, Bogacińska-Karaś M, Kuźmicz K, Rola R, Albrecht J. Downregulation of GLS2 in glioblastoma cells is related to DNA hypermethylation but not to the p53 status. Mol Carcinog. 2016 Sep;55(9):1309-16. doi: 10.1002/mc.22372. praca oryginalna.
  • Albrecht J, Zielińska M. Mechanisms of Excessive Extracellular Glutamate Accumulation in Temporal Lobe Epilepsy. Neurochem Res. 2017 Jun;42(6):1724-1734. doi: 10.1007/s11064-016-2105-8.
  • Milewski K, Oria M. What we know: the inflammatory basis of hepatic encephalopathy. Metab Brain Dis (2016) 31:1239–1247. DOI 10.1007/s11011-015-9740-7.
  • Jęśko H, Wilkaniec A, Cieślik M, Hilgier W, Gąssowska M, Lukiw WJ, Adamczyk A1.Altered Arginine Metabolism in Cells Transfected with Human Wild-Type Beta   Amyloid Precursor Protein (βAPP).  Curr Alzheimer Res. (2016) 13(9):1030-9.
  • 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):1272-81. doi: 10.1111/jnc.13387.
  • 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.
  • 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 Sep;88:26-31. doi: 10.1016/j.neuint.2014.12.004.
  • 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. Szeliga, J. Albrecht. Opposing roles of glutaminase isoforms in determining glioblastoma cell phenotype. Neurochem. Int. 2015 Sep;88:6-9. doi: 10.1016/j.neuint.2014.11.004.
  • 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. 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, 88:20-5. doi: 10.1016/j.neuint.2014.10.006.
  • 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 Aug 8. doi: 10.1111/jnc.12823.
  • 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  (2014) Ammonia. In: Aminoff M.J. and Daroff R.B. (eds.) Encyclopedia of the Neurological Sciences, 2nd edition, vol. 1, pp. 148-151. Oxford: Academic Press.
  • 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.
  • 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.
  • 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. 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. 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.
  • 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, 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. 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.
  • 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):5466-9. doi: 10.1016/j.bmcl.2012.07.036.
  • 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. 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. Strużynska, 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.