Prof. Dr. med. Astrid Jeibmann

Institut für Neuropathologie

Pottkamp 2
Tel.: +49-(0)251-83-56976
Fax.: +49-(0)251-83-56971
Email
 

Neurotoxicology

Clinical features and prognosis of major neurological diseases, such as Alzheimer´s, Parkinson´s, traumatic injury and stroke, are not only determined by mechanics, cell biology and genetics, but are strongly affected by the patient´s environment and behavior, such as social interaction, cognitive and physical activity. In addition, environmental and nutritive toxins (heavy metals, smoking, alcohol, illicit drugs, medical substances, chronic stress) may affect the course of neurological disease and often harm the brain per se. We are interested in mechanisms of these lifestyle effects on the brain using rodent and invertebrate models as well as human brain tissue.

In cooperation with the group of Prof. Uwe Karst (Analytical Chemistry) we are currently studying abnormal deposition of silver (derived from silver-coated endoprostheses, fig. 1) and gadolinium (derived from MRI contrast agents, fig. 2) in human brain tissue and animal studies. Using Drosophila melanogaster we are studying the in-vivo distribution of arsenic-containing lipids that are included in seafood (fig. 3).
 

Figure 1: (top) Allocation of silver deposits to endothelial cells in the cerebellum of a patient with three silver-coated endoprostheses by means of high-resolution LA-ICP-MS (spot size 4 µm). a+b) Microscopic image of immunohistochemically stained parallel section. Dark-brownish structures indicate homogenously spread endothelial cells throughout all cortical cell layers. c) Elemental distribution maps of aluminum visualizing structural features of ablated areas. d) Gold (Au) signals correlate with corresponding dark-brownish stained cell types (endothelial cells in b) indicating a successful antibody-labelling. f) Overlays of elemental distribution maps of 107Ag (red, individually displayed in rainbow color code in e) and 197Au (green) demonstrate a correlation (yellow) of both elements in the case of endothelial cells.

Figure 2: (top) Analysis of the autopsy brain thin sections of a patient after administration of gadobutrol (Gadovist) 16 days before death. a-c) Microscopic image of the dentate nucleus (a), corresponding quantitative distribution map of gadolinium investigated by LA-ICP-MS (b) and overlay of the gadolinium (red) and phosphorus (green) distribution (c).

Figure 3: Gadolinium content and distribution in foot pads determined by laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) (C and D) in comparison to control (A and B) and changes of small fibers, stained for PGP9.5 (IENF) (E–G, I) and TAS (H–J). LA-ICP-MS analyses of foot pads (marked by dotted lines) treated with gadodiamide (C and D) show gadolinium in the dermis of the footpad in comparison to control foot pad treated with saline (A and B). Schematic overview of the dermis and epidermis with small fibers (depicted in green) as well as sweat glands and sweat gland ducts (E). Slightly reduced IENFD after administration of gadobutrol (G) and strongly decreased IENFD after administration of gadodiamide (I) in comparison to control (F). Schematic overview of the epidermis with TAS (H). Terminal axonal swellings are clearly detectable after gadodiamide administration (J) in comparison to control (inset). The highest TAS/IENFD that was found for gadodiamide caused a clear visual pattern that allowed a direct identification of the animals injected with gadodiamide based on the first visual inspection.
Figure 4: (top) Combined MALDI-MS and LA-ICPMS bioinaging. (a) Representative positive ion mode mass spectrum signal of molecular AsHC 332 at m/z 333.2120 (b)MALDI-MS image of the compound (c) LA-ICPMS image of the As distribution acquired from the same tissue slice after the MALDI-MS analysis. Prior to the analysis, the adult fly was fed with 50µM of AsHC 332 spiked feed (3,2 µg As/g) for 3 days. (d) Microscopic image of the analyzed section of the adult fly. *unknown substance.

Cooperations:

Prof. Dr. Julia Bornhorst
Bergische Universität Wuppertal
Lehrstuhl für Lebensmittelchemie
Gaußstr. 20, 42119 Wuppertal, Germany

Prof. Dr. Uwe Karst
University of Münster
Institute of Inorganic and Analytical Chemistry
Corrensstraße 30
48149 Münster, Germany

Prof. Dr. med., ass. jur. Alexander Radbruch
Klinik für Neuroradiologie
Universitätsklinikum Bonn
Venusberg-Campus 1, 53127 Bonn, Germany

Dr. med. vet., Dipl. SVLAS, Henning Richter
Diagnostic Imaging Research Unit (DIRU)
Clinic for Diagnostic Imaging
Department of Clinical Diagnostics and Services
Vetsuisse Faculty
University of Zurich, Switzerland

PD Dr. med. Anne Schänzer
Institute of Neuropathology
University Clinic Giessen and Marburg
Arndtstr. 16, 35392 Giessen, Germany

Prof. Dr. Tanja Schwerdtle,
Institut für Ernährungswissenschaft
Abteilung Lebensmittelchemie
Arthur-Scheunert-Allee 114-116
14558 Nuthetal, OT Bergholz-Rehbrücke, Germany

PD Dr. rer. nat. Christoph van Thriel
Department of Toxicology
Leibniz Research Centre for Working Environment
and Human Factors (IfADo)
Dortmund, Germany

Selected Publications:

  1. Richter H, Bücker P, Martin LF, Dunker C, Fingerhut S, Xia A, Karol A, Sperling M, Karst U, Radbruch A, Jeibmann A.
    Gadolinium Tissue Distribution in a Large-Animal Model after a Single Dose of Gadolinium-based Contrast Agents. Radiology 2021 Sep 21:210553. doi: 10.1148/radiol.2021210553. Online ahead of print. PMID: 34546128
     
  2. Bücker P, Richter H, Radbruch A, Sperling M, Brand M, Holling M, Van Marck V, Paulus W, Jeibmann A, Karst U.
    Deposition patterns of iatrogenic lanthanum and gadolinium in the human body depend on delivered chemical binding forms. J Trace Elem Med Biol. 2021 Jan;63:126665. doi: 10.1016/j.jtemb.2020.126665. Epub 2020 Oct 24. PMID: 33152670
     
  3. Radbruch A, Richter H, Bücker P, Berlandi J, Schänzer A, Deike-Hofmann K, Kleinschnitz C, Schlemmer HP, Forsting M, Paulus W, Martin LF, van Thriel C, Karst U, Jeibmann A.
    Is Small Fiber Neuropathy Induced by Gadolinium-Based Contrast Agents? Invest Radiol. 2020 Aug;55(8):473-480. doi: 10.1097/RLI.0000000000000677. PMID: 32604384
     
  4. Radbruch A, Richter H, Fingerhut S, Martin LF, Xia A, Henze N, Paulus W, Sperling M, Karst U, Jeibmann A.
    Gadolinium Deposition in the Brain in a Large Animal Model: Comparison of Linear and Macrocyclic Gadolinium-Based Contrast Agents. Invest Radiol. 2019 Sep;54(9):531-536. doi: 10.1097/RLI.0000000000000575. PMID: 31261291
     
  5. Clases D, Fingerhut S, Jeibmann A, Sperling M, Doble P, Karst U.
    LA-ICP-MS/MS improves limits of detection in elemental bioimaging of gadolinium deposition originating from MRI contrast agents in skin and brain tissues. J Trace Elem Med Biol. 2019 Jan;51:212-218. doi: 10.1016/j.jtemb.2018.10.021. Epub 2018 Nov 1. PMID: 30466933
     
  6. Fingerhut S, Sperling M, Holling M, Niederstadt T, Allkemper T, Radbruch A, Heindel W, Paulus W, Jeibmann A, Karst U.
    Gadolinium-based contrast agents induce gadolinium deposits in cerebral vessel walls, while the neuropil is not affected: an autopsy study. Acta Neuropathol. 2018 Jul;136(1):127-138. doi: 10.1007/s00401-018-1857-4. Epub 2018 May 10. PMID: 29748901
     
  7. Fingerhut S, Niehoff AC, Sperling M, Jeibmann A, Paulus W, Niederstadt T, Allkemper T, Heindel W, Holling M, Karst U.
    Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents. J Trace Elem Med Biol. 2018 Jan;45:125-130. doi: 10.1016/j.jtemb.2017.10.004. Epub 2017 Oct 13. PMID: 29173468
     

Contact:
Astrid Jeibmann (Email) and Werner Paulus (Email)

 

 

Special model: Drosophila melanogaster

Drosophila melanogaster as model in neuroscience and neuropathology

We strongly feel that Drosophila represents a fascinating and extremely versatile model for studying pathogenesis of neurological disease as well as for exploring interactions between brain, behavior and environment. This is the reason why we have established a Drosophila lab in our institute building. We are experimentally using the fly in various areas, including neurooncology, neurodegeneration, neurotoxicology and lifestyle neuropathology.
Drosophila melanogaster, as a model organism, offers several advantages, including easy handling, rapid generation time, low cost, and a wide armamentarium of genetic techniques. Many molecular pathways are conserved between invertebrates and humans. Furthermore, Drosophila can be used in neuropharmacological experiments because this organism is amenable to external/food application, inhalation, or injection of substances in a large number of wild type or mutant animals.

Figure 1: The Drosophila lab in the Institute of Neuropathology

Selected publications:

  1. Berlandi J, Chaouch A, De Jay N, Tegeder I, Thiel K, Shirinian M, Kleinman CL, Jeibmann A, Lasko P, Jabado N, Hasselblatt M
    Identification of genes functionally involved in the detrimental effects of mutant histone H3.3-K27M in Drosophila melanogaster. Neuro Oncol. 2019 Jan 23. doi: 10.1093/neuonc/noz021. [Epub ahead of print]
     
  2. Tegeder I, Thiel K, Erkek S, Johann PD, Berlandi J, Thatikonda V, Frühwald MC, Kool M, Jeibmann A, Hasselblatt M
    Functional relevance of genes predicted to be affected by epigenetic alterations in atypical teratoid/rhabdoid tumors. J Neurooncol. 2019 Jan;141(1):43-55
     
  3. Ruland C, Berlandi J, Eikmeier K, Weinert T, Lin FJ, Ambree O, Seggewiss J, Paulus W, Jeibmann A
    Decreased Cerebral Irp-1B Limits Impact of Social Isolation in Wildtype and Alzheimer's Disease Modelled in Drosophila melanogaster. Genes Brain Behav. 2018 Jun;17(5):e12451
     
  4. Berlandi J, Lin FJ, Ambrée O, Rieger D, Paulus W, Jeibmann A
    Swing Boat: Inducing and Recording Locomotor Activity in a Drosophila melanogaster Model of Alzheimer's Disease. Front Behav Neurosci. 2017 Aug 30;11:159
     
  5. Niehoff AC, Schulz J, Soltwisch J, Meyer S, Kettling H, Sperling M, Jeibmann A, Dreisewerd K, Francesconi KA, Schwerdtle T, Karst U
    Imaging by Elemental and Molecular Mass Spectrometry Reveals the Uptake of an Arsenolipid in the Brain of Drosophila melanogaster. Anal Chem. 2016 May 17;88(10):5258-63
     
  6. Niehoff AC, Bauer OB, Kröger S, Fingerhut S, Schulz J, Meyer S, Sperling M, Jeibmann A, Schwerdtle T, Karst U
    Quantitative Bioimaging to Investigate the Uptake of Mercury Species in Drosophila melanogaster. Anal Chem. 2015 Oct 20;87(20):10392-6
     
  7. Meyer S, Schulz J, Jeibmann A, Taleshi MS, Ebert F, Francesconi KA, Schwerdtle T
    Arsenic-containing hydrocarbons are toxic in the in vivo model Drosophila melanogaster. Metallomics. 2014 Nov;6(11):2010-4
     
  8. Jeibmann A, Halama K, Witte HT, Kim SN, Eikmeier K, Koos B, Klämbt C, Paulus W
    Involvement of CD9 and PDGFR in migration is evolutionarily conserved from Drosophila glia to human glioma. J Neurooncol. 2015 Sep;124(3):373-83
     
  9. Kim SN, Jeibmann A, Halama K, Witte HT, Wälte M, Matzat T, Schillers H, Faber C, Senner V, Paulus W, Klämbt C
    ECM stiffness regulates glial migration in Drosophila and mammalian glioma models. Development. 2014 Aug;141(16):3233-42
     
  10. Jeibmann A, Eikmeier K, Linge A, Kool M, Koos B, Schulz J, Albrecht S, Bartelheim K, Frühwald MC, Pfister SM, Paulus W, Hasselblatt M
    Identification of genes involved in the biology of atypical teratoid/rhabdoid tumours using Drosophila melanogaster. Nat Commun. 2014 Jun 3;5:4005
     
  11. Witte HT, Jeibmann A, Klämbt C, Paulus W
    Modelling glioma growth and invasion in Drosophila melanogaster. Neoplasia. 2009 Sep;11(9):882-8
     
  12. Jeibmann A, Paulus W
    Drosophila melanogaster as model organism of brain diseases. Int J Mol Sci. 2009 Feb;10(2):407-40
     

Contact:
Astrid Jeibmann (Email)