Aktuellste Publikationen

Nutrients. 2021 Mar 18;13(3):985.doi: 10.3390/nu13030985.

Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice.

Luisa Müller  1   2   3 Nicole Power Guerra  1 Jan Stenzel  4 Claire Rühlmann  1 Tobias Lindner  4

Bernd J Krause  4   5 Brigitte Vollmar  1   4 Stefan Teipel  2   3   6 Angela Kuhla  1   3 .

1 Rudolf-Zenker-Institute for Experimental Surgery, Medical University Rostock, 18057 Rostock, Germany.

2 Department of Psychosomatic Medicine and Psychotherapy, University of Rostock, 18147 Rostock, Germany.

3 Centre for Transdisciplinary Neurosciences Rostock (CTNR), University of Rostock, 18147 Rostock, Germany.

4 Core Facility Multimodal Small Animal Imaging, Rostock University Medical Center, 18057 Rostock, Germany.

5 Department of Nuclear Medicine, Rostock University Medical Center, 18057 Rostock, Germany.

6 German Center for Neurodegenerative Diseases (DZNE)-Rostock/Greifswald, 18147 Rostock and 17489 Greifswald, Germany.

Abstract

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer's disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism-a hallmark of AD-and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology. 

 

 

Cancers (Basel) 2021 May 19;13(10):2483.doi: 10.3390/cancers13102483.

Multimodal Imaging Techniques to Evaluate the Anticancer Effect of Cold Atmospheric Pressure Plasma

Marcel Kordt  1 Isabell Trautmann  1 Christin Schlie  1 Tobias Lindner  2 Jan Stenzel  2 Anna Schildt  2 ,           Lars Boeckmann  3 Sander Bekeschus  4 Jens Kurth  5 Bernd J Krause  2   5 Brigitte Vollmar  1 Eberhard Grambow  1   6

1 Rudolf-Zenker-Institute of Experimental Surgery, Rostock University Medical Center, 18057 Rostock, Germany.

2 Core Facility Multimodal Small Animal Imaging, Rostock University Medical Center, 18057 Rostock, Germany.

3 Clinic and Policlinic for Dermatology and Venereology, Rostock University Medical Center, 18057 Rostock, Germany.

4 Center for innovation competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP), 17489 Greifswald, Germany.

5 Department of Nuclear Medicine, Rostock University Medical Center, 18055 Rostock, Germany.

6 Department for General, Visceral-, Vascular- and Transplantation Surgery, Rostock University Medical Center, 18057 Rostock, Germany.

Abstract

Background: Skin cancer is the most frequent cancer worldwide and is divided into non-melanoma skin cancer, including basal cell carcinoma, as well as squamous cell carcinoma (SCC) and malignant melanoma (MM).

Methods: This study evaluates the effects of cold atmospheric pressure plasma (CAP) on SCC and MM in vivo, employing a comprehensive approach using multimodal imaging techniques. Longitudinal MR and PET/CT imaging were performed to determine the anatomic and metabolic tumour volume over three-weeks in vivo. Additionally, the formation of reactive species after CAP treatment was assessed by non-invasive chemiluminescence imaging of L-012. Histological analysis and immunohistochemical staining for Ki-67, ApopTag®, F4/80, CAE, and CD31, as well as protein expression of PCNA, caspase-3 and cleaved-caspase-3, were performed to study proliferation, apoptosis, inflammation, and angiogenesis in CAP-treated tumours.

Results: As the main result, multimodal in vivo imaging revealed a substantial reduction in tumour growth and an increase in reactive species after CAP treatment, in comparison to untreated tumours. In contrast, neither the markers for apoptosis, nor the metabolic activity of both tumour entities was affected by CAP.

Conclusions: These findings propose CAP as a potential adjuvant therapy option to established standard therapies of skin cancer.

 

 

Biomedicines 2020 Dec 9;8(12):587.doi: 10.3390/biomedicines8120587.

Dietary-Induced Low-Grade Inflammation in the Liver

Nicole Power Guerra  1 Luisa Müller  1   2 Kristin Pilz  3 Annika Glatzel  1 Daniel Jenderny  1 Deborah          Janowitz  3 Brigitte Vollmar  1 Angela Kuhla  1

1 Rudolf-Zenker-Institute for Experimental Surgery, Medical University Rostock, 18057 Rostock, Germany.

2 Department of Psychosomatic Medicine and Psychotherapy, University of Rostock, 18147 Rostock, Germany.

3 Department of Psychiatry, University of Greifswald, 17489 Greifswald, Germany.

Abstract

The literature describes a close correlation between metabolic disorders and abnormal immune responses, like low-grade inflammation (LGI), which may be one mechanistic link between obesity and various comorbidities, including non-alcoholic fatty liver disease (NAFLD). In our study, we investigated the influence of dietary composition on obesity-derived LGI in the liver. We used a dietary induced obesity mouse model of C57BL/6J mice fed with high fat diet (HFD, 60% fat, 20% protein, 20% carbohydrates) and two different controls. One was rich in carbohydrates (10% fat, 20% protein, 70% carbohydrates), further referred to as the control diet (CD), and the other one is referred to as the standard diet (SD), with a more balanced macronutrient content (9% fat, 33% protein, 58% carbohydrates). Our results showed a significant increased NAFLD activity score in HFD compared to both controls, but livers of the CD group also differed in their macroscopic appearance from healthy livers. Hepatic fat content showed significantly elevated cholesterol concentrations in the CD group. Histologic analysis of the cellular immune response in the liver showed no difference between HFD and CD and expression analysis of immunologic mediators like interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor alpha also point towards a pro-inflammatory response to CD, comparable to LGI in HFD. Therefore, when studying diet-induced obesity with a focus on inflammatory processes, we encourage researchers to carefully select controls and not use a control diet disproportionally rich in carbohydrates.