Department of Neurotoxicology

Head:

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

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Secretary:

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

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Research staff

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

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

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

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

Krzysztof Milewski PhD - 22 60 86 416, This email address is being protected from spambots. You need JavaScript enabled to view it.

Mariusz Popek,  PhD – 22 60 86 442, This email address is being protected from spambots. You need JavaScript enabled to view it.

Katarzyna Skowrońska, PhD – 22 60 86 442, This email address is being protected from spambots. You need JavaScript enabled to view it.

 

PhD Students

Karolina Orzeł , M.Sc., Ing., - 22 60 86 442, This email address is being protected from spambots. You need JavaScript enabled to view it.

Marek Pawlik, , M.Sc., Ing. , - 22 60 86 441, This email address is being protected from spambots. You need JavaScript enabled to view it.

Borzęcki Krzysztof , M.Sc. - 22 60 86 441, 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 86 417; 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

"The role of aquaporin 4 in cerebral edema in murine model of acute hepatic encephalopathy and regulation of aquaporin 4 expression and/or localisation by caveolin 1 and p38 MAP kinase."Grant NCN Miniatura 3 No 2019/03/X/NZ4/00623, principal investigator: PhD Marta Obara-Michlewska (2019-2020)

"Role of astrocytic NMDA receptors in the regulation of glutamine synthetase activity in cultured mouse astrocytes. Attempt at defining intraastrocytic signaling pathways." Grant NCN Preludium 14 no 2017/27/N/NZ3/02819, principal investigator: Msc. Ing. Katarzyna Skowrońska(2018-2020)

"Peroxiredoxins as potential therapeutic targets in glioblastoma".grant NCN Opus 13 No 2017/25/B/NZ7/00388, principal investigator: PhD Monika Szeliga (2018-2020)

"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/B/NZ4/03678, principal investigator: Prof. PhD Jan Albrecht (2017-2020)

"BLOOD-BRAIN BARIER IMPAIRMENT IN HEPATIC ENCEPHALOPATHY: ROLE OF MICRO RNA.” Grant NCN OPUS 10 no 2015/19/B/NZ4/01902, principal investigator: Prof. PhD Magdalena Zielińska (2016-2020)

"Role of Sp1 transcription factor in the regulation of astrocytic glutamine transporter SN1 expression: effect of ammonia and astrocyte-neuron interactions", grant NCN Preludium 11, no 2016/21/N/NZ4/03759, principal investigator M.sc.Ing. Katarzyna Dabrowska (2017-2020)

"Proteinkinase B signalling pathway in glioblastoma cells transfected with sequence encoding liver-type glutaminase (GAB)" grant NCN Preludium 12 no 2016/23/N/NZ5/01428, principal investigator M.sc. Ing. Ewelina Majewska (2017-2019)

”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 PhD Anna Czarnecka (2017-2018)

“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 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)

THE ROLE OF ASSYMETRIC DIMETHYLARGININE (ADMA) IN HEPATHIC ENCEPHALOPATHY: MARKER, MEDIATOR OR MODULATOR?” Grant NCN no 2013/09/B/NZ4/00536, principal investigator PhD 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: Phd Monika Szeliga (2014-2017)

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)

 Cooperation:

  • Faculty of Life Science, University of Manchester, UK (prof. Alexei Verkhratsky)
  • The Biotechnology Centre of Oslo, University of Oslo, Norway (prof. Farrukh A. Chaudhry)
  • Institute of Pharmacology, Polish Academy of Sciences (prof. Grzegorz Hess )
  • Faculty of Sciences, University of Málaga, Spain (prof. Javier Marquez)
  • The Children’s Memorial Health Institute (dr Dariusz Rokicki)
  • Instytut Medycyny Wsi, Lublin (prof. Waldemar A. Turski)
  • Medical University of Lublin (prof. Stanisław Czuczwar)

 

List of publications since 2012

  • Pawlik MJ, Obara-Michlewska M, Popek MP, Czarnecka AM, Czuczwar SJ, Łuszczki J, Kołodziej M, Acewicz A, Wierzba-Bobrowicz T, Albrecht J.  Pretreatment with a glutamine synthetase inhibitor MSO delays the onset of initial seizures induced by pilocarpine in juvenile rats. Brain Res. 2021 Jan 7;147253. DOI: 10.1016/j.brainres.2020.147253
  • Majewska E, Márquez J, Albrecht J, Szeliga M. Transfection with GLS2 Glutaminase (GAB) Sensitizes Human Glioblastoma Cell Lines to Oxidative Stress by a Common Mechanism Involving Suppression of the PI3K/AKT Pathway. Cancers (Basel). 2019 Jan 19;11(1). pii: E115. doi: 10.3390/cancers11010115.
  • Dąbrowska K, Zielińska MSilencing of Transcription Factor Sp1 Promotes SN1 Transporter Regulation by Ammonia in Mouse Cortical Astrocytes. Int J Mol Sci. 2019 Jan 9;20(2). pii: E234. doi: 10.3390/ijms20020234.
  • Dąbrowska K, Albrecht J, Zielińska M.Protein kinase C-mediated impairment of glutamine outward transport and SN1 transporter distribution by ammonia in mouse cortical astrocytes. Neurochem Int. 2018 Sep;118:225-232. doi: 10.1016/j.neuint.2018.07.001. Epub 2018 Jul 3.
  • Zielińska M, Aschner M. 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, 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. Epub 2016 Sep 8.
  • 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. Epub 2016 Jan 22.
  • 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. Epub 2015 Nov 12.
  • 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. Epub 2015 Oct 15.
  • 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. Epub 2016 Nov 21.
  • 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.
  • 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.
  • Milewski K, Hilgier W, Albrecht J, Zielińska M. 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. Epub 2014 Dec 15.
  • Ruszkiewicz J, Albrecht J. 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. Epub 2014 Aug 27.
  • Szeliga M, Albrecht J 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. Epub 2014 Dec 18.
  • Ruszkiewicz J, Albrecht JChanges in the mitochondrial antioxidant systems in neurodegenerative diseases and acute brain disorders. Neurochem Int. 2015 Sep;88:66-72. doi: 10.1016/j.neuint.2014.12.012. Epub 2015 Jan 6.
  • Albrecht J, Zielińska M. 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 Nov;131(3):265-7. doi: 10.1111/jnc.12823. Epub 2014 Aug 8.
  •  Zielińska M, Obara-Michlewska M, Hilgier W, Albrecht J. Citrulline uptake in rat cerebral cortex slices: modulation by Thioacetamide -Induced hepatic failure. Metab Brain Dis. 2014 Dec;29(4):1053-60. doi: 10.1007/s11011-013-9472-5. Epub 2014 Jan 3.
  • 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.
  • Zielińska M, Popek M, Albrecht J. Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept. Neurochem Res. 2014;39(3):599-604. doi: 10.1007/s11064-013-1141-x. Epub 2013 Sep 26.
  •  Martín-Rufián M, Nascimento-Gomes R, Higuero A, Crisma AR, Campos-Sandoval JA, Gómez-García MC, Cardona C, Cheng T, Lobo C, Segura JA, Alonso FJ, Szeliga M, Albrecht J, Curi R, Márquez J, Colquhoun A, Deberardinis RJ, Matés JM. Both GLS silencing and GLS2 overexpression synergize with oxidative stress against proliferation of glioma cells. J Mol Med (Berl). 2014 Mar;92(3):277-90. doi: 10.1007/s00109-013-1105-2. Epub 2013 Nov 26.
  • Szeliga M, Zgrzywa A, Obara-Michlewska M, Albrecht J.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 Nov;123(3):428-36. doi: 10.1111/j.1471-4159.2012.07917.x. Epub 2012 Sep 21.
  • Juszczak M, Matysiak J, Szeliga M, Pożarowski P, Niewiadomy A, Albrecht J, Rzeski W. 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 Sep 1;22(17):5466-9. doi: 10.1016/j.bmcl.2012.07.036. Epub 2012 Jul 20.
  • Skowrońska M, Zielińska M, Wójcik-Stanaszek L, Ruszkiewicz J, Milatovic D, Aschner M, Albrecht J. Ammonia increases paracellular permeability of rat brain endothelial cells by a mechanism encompassing oxidative/nitrosative stress and activation of matrix metalloproteinases. J Neurochem. 2012 Apr;121(1):125-34. doi:10.1111/j.1471-4159.2012.07669.x. Epub 2012 Feb 15.
  • Skowrońska M, Albrecht J. Alterations of blood brain barrier function in hyperammonemia: an overview. Neurotox Res. 2012 Feb;21(2):236-44. doi: 10.1007/s12640-011-9269-4. Epub 2011 Aug 27.
  • Hilgier W, Łazarewicz JW, Strużynska L, Frontczak-Baniewicz M, Albrecht J.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 Jan;33(1):16-22. doi: 10.1016/j.neuro.2011.10.005. Epub 2011 Oct 21.