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Experimental Neuroimmunology

An immune response is part of most neurological diseases, and the development of late-onset Alzheimer's Disease (AD) has been linked to immune related genes and most recently also to epigenetic modifications. This indicates a significant contribution of immunity to AD pathology. The immune response during AD is largely mediated by the brain's resident macrophages, the microglia, which are attracted to and surround Aβ deposits in the AD brain. However, various aspects of their role in amyloid plaque homeostasis and AD pathogenesis remain unclear. Furthermore, how inflammation in the periphery may affect the immune response in the brain remains incompletely understood.

Main objectives
Recent results
Staff
Publications

1. To understand how microglia contribute to AD pathology and in particular to Aβ plaque formation and Aβ clearance.

2. To investigate how peripheral inflammatory stimuli alter central immunity, and how this may affect the pathogenesis of AD as well as other neurodegenerative diseases and stroke.

To this end we analyze Aβ precursor protein- (APP) transgenic mouse lines that are deficient in a variety of immune-related molecules, that allow the temporary ablation of microglia, or after peripheral immune stimulation. We isolate microglia from adult and aged brains and study their phagocytic behavior and inflammatory responses in culture. Together with the molecular imaging group we use multiphoton imaging to study microglial behavior in the aging brain and in APP transgenic mice.

In the Neuroimmunology group, we previously found that short-term ablation (3-4 weeks) of microglia in APP x CD11b-HSVTK mice did not significantly affect plaque homeostasis (Grathwohl et al., Nat Neurosci 2009). Interestingly, when analyzing the CD11b-HSVTK strain, we found that the microglia-depleted brain is rapidly repopulated by peripheral monocytes, revealing a strong homeostatic drive for the presence of a myeloid population in the CNS (Varvel et al., PNAS 2012). This model can now be exploited to study the effect of replacing resident microglia with peripheral monocytes in animal models of AD pathology.

In addition, we have recently shown that, after brain ischemia, microglia execute neuronal death through the phagocytic uptake of stressed-but-viable neurons (Neher et al., PNAS 2013). This indicates novel therapeutic approaches for the prevention of delayed neuronal loss after stroke and possibly in neurodegenerative diseases.

Contact: Jonas Neher

 

 


 
Name
Department
Phone
Email
 Desirée Brösamle
Desirée Brösamle PhD Student
Experimental Neuroimmunology
07071 91-54352 
 Julia Koppelmann
Julia Koppelmann Master Student
Experimental Neuroimmunology
 
Dr. Jonas Neher
Dr. Jonas Neher Research Group Leader (DZNE)
Experimental Neuroimmunology
07071 29-87596 
 Linda Oberle
Linda Oberle Medical doctoral student
Experimental Neuroimmunology
07071 29-81951 
 Lisa Steinbrecher
Lisa Steinbrecher PhD Student
Experimental Neuroimmunology
07071 29-81945 
 Jessica Wagner
Jessica Wagner PhD Student (DZNE)
Experimental Neuroimmunology
07071 29-81945 
 Katleen Wild
Katleen Wild Technical Assistant (DZNE)
Experimental Neuroimmunology
07071 29-81951 

Jonas J Neher, Colm Cunningham (2019)  Priming Microglia for Innate Immune Memory in the BrainTrends in immunology 40:  358-374 (Abstract)

Wendeln AC, Degenhardt K, Kaurani L, Gertig M, Ulas T, Jain G, Wagner J, Häsler LM, Wild K, Skodras A, Blank T, Staszewski O, Datta M, Centeno TP, Capece V, Islam MR, Kerimoglu C, Staufenbiel M, Schultze JL, Beyer M, Prinz M, Jucker M, Fischer A, Neher JJ (2018) Innate immune memory in the brain shapes neurological disease hallmarks. Nature 556:332-338 (Abstract)

Varvel NH, Grathwohl SA, Degenhardt K, Resch C, Bosch A, Jucker M, Neher JJ. Replacement of brain-resident myeloid cells does not alter cerebral β-amyloid desposition in mouse models of Alzheimer´s disease. J Ex Med 212:1803-9 (Abstract)

Brown GC, Neher JJ (2014) Microglial phagocytosis of live neuronsNat Rev Neurosci 15:209-16 (Abstract)

Neher JJ, Emmrich JV, Fricker M, Mander PK, Théry C, Brown GC (2013) Phagocytosis executes delayed neuronal death after focal brain ischemiaProc Natl Acad Sci USA 110:E4098-107 (Abstract)

Research group leader
Dr. Jonas Neher jonas.neheruni-tuebingen.de Address

Center of Neurology
Hertie Institute for Clinical Brain Research
Department Cellular Neurology

Otfried-Müller-Straße 27
72076 Tübingen

Phone: +49 (0)7071 925-4351

list of publications