Laboratory of Preclinical Research and Environmental Agents

Head
Prof. Robert Strosznajder, Ph.D. phone: +48 22 60 86 411, This email address is being protected from spambots. You need JavaScript enabled to view it.

Research staff
Ewa Koźniewska-Kołodziejska, Prof., Ph.D., phone: +48 22 60 86 489, This email address is being protected from spambots. You need JavaScript enabled to view it.
Kinga Czubowicz, Ph.D., phone: +48 22 60 86 461, This email address is being protected from spambots. You need JavaScript enabled to view it.
Przemysław Wencel, Ph.D., phone: +48 22 60 86 461, This email address is being protected from spambots. You need JavaScript enabled to view it.
Marta Aleksandrowicz Ph.D., phone: +48 22 60 86 566, This email address is being protected from spambots. You need JavaScript enabled to view it.
Łukasz Przykaza, Ph.D., phone: +48 22 60 86 423, lThis email address is being protected from spambots. You need JavaScript enabled to view it.
Żanna Pastuszak-Stępień, Ph.D., phone: +48 22 60 86 423, This email address is being protected from spambots. You need JavaScript enabled to view it.


PhD students
Iga Wieczorek M.Sc., phone: +48 22 60 86 461,This email address is being protected from spambots. You need JavaScript enabled to view it.

Research profile

  • The study of molecular mechanisms of selected pharmacologically active compounds in aging processes, neurodegenerative diseases with a special focus on Alzheimer's disease and in the pathology of type 2 diabetes and obesity.
  • Involvement of poly (ADP-ribose) polymerase (PARP-1) and sirtuins (histone deacetylases class III) in the pathomechanism of neurodegenerative disorders.
  • Study of the role of PARP inhibitors and sirtuin activators in ceramide-induced cytotoxicity.
  • The role of S1P signaling in type 2 diabetes pathology and obesity.
  • The role of bioactive sphingolipids: ceramide, ceramide-1-phosphate and sphingosine-1-phosphate in the selected models of oxidative stress.
  • Impairment of the regulation of cerebral vessels and brain function in experimental hyponatremia.
  • Evaluation of the neuroprotective potential of Y2 receptor agonists in a rat model of focal stroke - cerebral ischemia/reperfusion.

Grants

  • Mechanisms and consequences of small cerebral blod vessels dysfunction in experimental hyponatremia in the presence of vasopressin, NCN 2021/43/D/NZ4/03304, Head of project: Marta Aleksandrowicz, Ph.D., Duration of the project: 2022-2025.
  • Potential neuroprotective properties of modulators of sphingosine-1-phosphate(S1P) receptors (fingolimod and siponimod) in toxicity of amyloid beta oligomers:The significance of S1P receptors in Alzheimer’s disease, 2021/41/N/NZ5/02036, Head of project: Iga Wieczorek, M.Sc., Scientific mentor: Robert Piotr Strosznajder, Prof., Ph.D.; Duration of the project: 2022-2024.
  • Searching for the background underlying the neuroprotective effects of the specific agonist of Y2 receptors - NPY(13-36) in the model of transient, focal cerebral ischemia in rats, NCN 2019/33/N/NZ4/02894, Head of project: Łukasz Przykaza, Ph.D., Scientific mentor: Ewa Kozniewska, Ph.D., Professor, Duration of the project: 2020-2023.
  • The role of sphingosine kinases/sphingosine-1-phosphate dependent signaling in mice brains exposed to type II diabetes mellitus and high-fat diet. Searching for potential neuroprotective effects of fingolimod and metformin. NCN 2018/29/N/NZ4/00616 Head of project: Przemysław Leonard Wencel, Ph.D.; Scientific mentor: Robert Piotr Strosznajder, Prof., Ph.D.; Duration of the project: 2019-2022.
  • Effect of acute hyponatremia associated with vasopressin on the tone of the penetrating arterioles and the middle cerebral artery of the rat, 2017/01/X/N24/016022017, Head of project: Marta Aleksandrowicz, Ph.D., Duration of the project: 2018-2019.
  • The role of bioactive sphingolipids: ceramide, ceramide-1-phosphate and sphingosine-1-phospahte in regulation of mitochondria and synaptic function in experimental models of Alzheimer disease (AD). The non-amyloid targets in AD therapy. NCN 2014/15/B/NZ3/01049, Head of project: Robert Piotr Strosznajder, Assoc. Prof., Ph.D., Duration of the project: 2015-2019.
  • The role of ceramide and sphingosine-1-phosphate receptor signalling in amyloid beta precursor protein metabolism. NCN 2013/11/N/NZ4/02233, Head of project: Kinga Czubowicz, Ph.D., Scientific mentor: Robert Piotr Strosznajder, Assoc. Prof., Ph.D., Duration of the project: 2014-2017.

Collaboration
domestic
• Mossakowski Medical Research Centre, Laboratory of Pathoneurochemistry, Warsaw.
• Mossakowski Medical Research Centre, Department of Cellular Signalling, Warsaw.
• Mossakowski Medical Research Centre, Electron Microscopy Platform, Warsaw.
• Military Medical Institute, Central Clinical Hospital MON, Neurological Clinic, Warsaw.
foreign
• University of Basel, Neurobiology Laboratory for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular and Cognitive Neuroscience, Basel, Switzerland.
• LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, USA.
• Institute of Neurobiology, Slovak Academy of Sciences, Košice, Slovak Republic.
• University Graduate School of Medicine, Department of Molecular and Cellular Biology, Kobe, Division of Biochemistry, Kobe, Japan.
• University of Catania, Department of Biochemistry, Faculty of Medicine, Catania, Italy.

Research equipment

  • SimpliAmpTM Thermal Cycler (Applied Biotechnology);
  • electrophoresis and protein transfer equipment (Bio-Rad);
  • LDF – DRT4 Moor Instrument;
  • Microscope Olympus SZX16;
  • Microscope Olympus CKX 41/Olympus CKX 53;
  • centrifuges, models: 5424 and 5430 R (Eppendorf) and MPW 211;
  • analytical balance (Radwag and FR-300), water bath (GFL), and other laboratory equipment.

Research methods
• Immunochemical (electrophoresis and immunodetection of proteins by Western blot method).
• Selected methods of molecular biology (RNA isolation, RT-PCR, qRT-PCR).
• Biochemical (measurements of enzyme activity and kinetics).
• Pharmacological (application of selected neuroprotective compounds, including inhibitors/activators of tested enzymes in in vivo and in vitro studies).
• analysis of lipid peroxidation and protein oxidation by spectrophotometric methods
• analysis of muse and rat’s behavior using: open field test, novel object recognition test, elevated plus maze test.

Experimental models in vivo:
• mouse transgenic model of Alzheimer’s disease (FVB/APP KM670/671NL);
• mouse sporadic model of Alzheimer's disease (C57BL / 6, streptozotocin model);
• mouse model of type 2 diabetes (C57BL / 6, high-fat diet plus low doses of streptozotocin);
• mice model of obesity (C57BL/6 mice after high-fat diet).
Experimental models in vitro:
• cell line PC12 – derived from rat adrenal gland pheochromocytoma;
• transfected cell line PC12 stably expressing human wild-type APP gene;
• transfected cell line PC12 stably expressing human APP gene with double Swedish mutation (K670M/N671L);
• cell line HT22 – immortalized mouse hippocampal neurons;
• cell line SH-SY5Y – derived from human neuroblastoma.

Selected publications

  • Wencel PL, Blecharz-Klin K, Piechal A, Pyrzanowska J, Mirowska-Guzel D, Strosznajder RP. Fingolimod Modulates the Gene Expression of Proteins Engaged in Inflammation and Amyloid-Beta Metabolism and Improves Exploratory and Anxiety-Like Behavior in Obese Mice. Neurotherapeutics. 2023 Jul 11. doi: 10.1007/s13311-023-01403-2. PMID: 37432552.
  • Wieczorek I, Strosznajder RP. Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration. Int J Mol Sci. 2023 Mar 24;24(7):6180. doi: 10.3390/ijms24076180. PMID: 37047151; PMCID: PMC10093903.
  • Klapczyńska K, Aleksandrowicz M, Koźniewska E. Role of the endothelial reverse mode sodium-calcium exchanger in the dilation of the rat middle cerebral artery during hypoosmotic hyponatremia. Pflugers Arch. 2023 Mar;475(3):381-390. doi: 10.1007/s00424-022-02770-z. Epub 2022 Nov 17. PMID: 36394650
  • Aleksandrowicz M, Kozniewska E. Hyponatremia as a risk factor for microvascular spasm following subarachnoid hemorrhage. Exp Neurol. 2022 Sep;355:114126. doi: 10.1016/j.expneurol.2022.114126. Epub 2022 May 30. PMID: 35654161
  • Przykaza Ł, Koźniewska E. Ligands of the Neuropeptide Y Y2 Receptors as a Potential Multitarget Therapeutic Approach for the Protection of the Neurovascular Unit Against Acute Ischemia/Reperfusion: View from the Perspective of the Laboratory Bench. Transl Stroke Res. 2022 Feb;13(1):12-24. doi: 10.1007/s12975-021-00930-4. Epub 2021 Jul 22. PMID: 34292517
  • Przykaza Ł. Understanding the Connection Between Common Stroke Comorbidities, Their Associated Inflammation, and the Course of the Cerebral Ischemia/Reperfusion Cascade. Front Immunol. 2021 Nov 15;12:782569. doi: 10.3389/fimmu.2021.782569. eCollection 2021. PMID: 34868060
  • Jęśko H, Wieczorek I, Wencel PL, Gąssowska-Dobrowolska M, Lukiw WJ, Strosznajder RP. Age-Related Transcriptional Deregulation of Genes Coding Synaptic Proteins in Alzheimer's Disease Murine Model: Potential Neuroprotective Effect of Fingolimod. Front Mol Neurosci. 2021 Jul 9;14:660104. doi: 10.3389/fnmol.2021.660104. PMID: 34305524; PMCID: PMC8299068.
  • Jęśko H, Wencel PL, Wójtowicz S, Strosznajder J, Lukiw WJ, Strosznajder RP. Fingolimod Affects Transcription of Genes Encoding Enzymes of Ceramide Metabolism in Animal Model of Alzheimer's Disease. Mol Neurobiol. 2020 Jun;57(6):2799-2811. doi: 10.1007/s12035-020-01908-3. Epub 2020 Apr 30. PMID: 32356173
  • Aleksandrowicz M, Kozniewska E. Compromised regulation of the rat brain parenchymal arterioles in vasopressin-associated acute hyponatremia. Microcirculation. 2020 Oct;27(7):e12644. doi: 10.1111/micc.12644. Epub 2020 Jul 14. PMID: 32603523
  • Czubowicz K, Jęśko H, Wencel P, Lukiw WJ, Strosznajder RP. The Role of Ceramide and Sphingosine-1-Phosphate in Alzheimer's Disease and Other Neurodegenerative Disorders. Mol Neurobiol. 2019 Aug;56(8):5436-5455. doi: 10.1007/s12035-018-1448-3. Epub 2019 Jan 5. PMID: 30612333
  • Jęśko H, Stępień A, Lukiw WJ, Strosznajder RP. The Cross-Talk Between Sphingolipids and Insulin-Like Growth Factor Signaling: Significance for Aging and Neurodegeneration. Mol Neurobiol. 2019 May;56(5):3501-3521. doi: 10.1007/s12035-018-1286-3. Epub 2018 Aug 23. PMID: 30140974
  • Jęśko H, Wencel PL, Lukiw WJ, Strosznajder RP. Modulatory Effects of Fingolimod (FTY720) on the Expression of Sphingolipid Metabolism-Related Genes in an Animal Model of Alzheimer's Disease. Mol Neurobiol. 2019 Jan;56(1):174-185. doi: 10.1007/s12035-018-1040-x. Epub 2018 Apr 23. PMID: 29687345