Lifestyle Neuropathology

 

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.

Using transgenic mouse models of Alzheimer´s disease, we have found that environmental enrichment and physical activity may improve behavioral, histological and molecular features of disease (Ambrée et al. 2006, Herring et al. 2011). 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. Using Drosophila melanogaster we are studying the in-vivo distribution of arsenic-containing lipids that are included in seafood (fig. 3). Finally, we explore Drosophila as a model for analyzing effects of sports activities versus physically inactive lifestyle (fig. 4) and social isolation versus social interaction (fig. 5) on normal and diseased brain.

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: (top) Combined MALDI-MS and LA-ICPMS bioimaging. (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 50 μM 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.

Figure 4: (top) Fruit flies in Drosophila activity monitor vials equipped with food (white) on the one side and stoppers (brown) on the other side. Activity is measured via infrared beam. (bottom) The device induces motor activity by tilting the fly vials repetitively at 3 pm during day time (yellow color). An activity peak is induced (blue box).

Figure 5: (top) Group housing of 20 flies in a big vial as well as single housing in a smaller vial. Flies are kept in a box, which prevents them to see each other. (bottom) Kaplan-Meier curves showing shorter survival of flies kept in single housing.

Cooperations:


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

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

Dr. Dirk Rieger
Lehrstuhl für Neurobiologie und Genetik
Biozentrum
Am Hubland
97074 Würzburg

 

Selected Publications:

  1. 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
     
  2. Ambrée O, Touma C, Görtz N, Keyvani K, Paulus W, Palme R, Sachser N.
    Activity changes and marked stereotypic behavior precede Abeta pathology in TgCRND8 Alzheimer mice. Neurobiol Aging. 2006 Jul;27(7):955-64.
     
  3. Herring A, Lewejohann L, Panzer AL, Donath A, Kröll O, Sachser N, Paulus W, Keyvani K.
    Preventive and therapeutic types of environmental enrichment counteract beta amyloid pathology by different molecular mechanisms. Neurobiol Dis. 2011 Jun;42(3):530-8.
     
  4. 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.
     
  5. 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.
     
  6. 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.
     
  7. Paulus W.
    Lifestyle neuropathology: how our behavior harms our brains and what we can do about it. Acta Neuropathol. 2014 Jan;127(1):1.
     

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