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
Arbeitsgruppe
Telefon
E-Mail
 Karoline Degenhardt
Karoline Degenhardt PhD Student
Experimental Neuroimmunology
07071 29-87607 
 Maren Lösch
Maren Lösch Technical Assistant
Experimental Neuroimmunology
07071-2986857 
Dr. Sonia Mazzitelli
Dr. Sonia Mazzitelli PostDoc
Experimental Neuroimmunology
07071 29-86853 
Dr. Jonas Neher
Dr. Jonas Neher Research Group Leader (DZNE)
Experimental Neuroimmunology
07071 29-87596 
 Jessica Wagner
Jessica Wagner PhD Student (DZNE)
Experimental Neuroimmunology
07071 29-81945 
 Ann-Christin Wendeln
Ann-Christin Wendeln PhD Student
Experimental Neuroimmunology
07071 29-81945 
 Katleen Wild
Katleen Wild Technical Assistant (DZNE)
Experimental Neuroimmunology
07071 29-81951 

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 neurons. Nat 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 ischemia. Proc Natl Acad Sci USA 110:E4098-107 (Abstract)

Varvel NH, Grathwohl SA, Baumann F, Liebig C , Bosch A, Brawek B, Thal DR, Charo IF, Heppner FL, Aguzzi A, Garaschuk O, Ransohoff RM, Jucker M (2012) Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells. Proc Natl Acad Sci USA 109:18150-5 (Abstract)

Forschungsgruppenleitung
Dr. Jonas Neher jonas.neheruni-tuebingen.de Anschrift

Zentrum für Neurologie
Hertie-Institut für klinische Hirnforschung
Abteilung Zellbiologie neurologischer Erkrankungen

Otfried-Müller-Straße 27
72076 Tübingen

Tel.: +49 (0)7071 29-87596
Fax: +49 (0)7071 29-4521

list of publications