TY  - JOUR
A1  - McFleder, Rhonda L.
A1  - Makhotkina, Anastasiia
A1  - Groh, Janos
A1  - Keber, Ursula
A1  - Imdahl, Fabian
A1  - Peña Mosca, Josefina
A1  - Peteranderl, Alina
A1  - Wu, Jingjing
A1  - Tabuchi, Sawako
A1  - Hoffmann, Jan
A1  - Karl, Ann-Kathrin
A1  - Pagenstecher, Axel
A1  - Vogel, Jörg
A1  - Beilhack, Andreas
A1  - Koprich, James B.
A1  - Brotchie, Jonathan M.
A1  - Saliba, Antoine-Emmanuel
A1  - Volkmann, Jens
A1  - Ip, Chi Wang
T1  - Brain-to-gut trafficking of alpha-synuclein by CD11c\(^+\) cells in a mouse model of Parkinson’s disease
JF  - Nature Communications
N2  - Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson’s disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c+ cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c\(^+\) cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c\(^+\) cells traffic from the brain to the ileum. Together these data provide a mechanism of αSyn trafficking between the brain and gut.
KW  - antigen-presenting cells
KW  - neuroimmunology
KW  - Parkinson's disease
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357696
VL  - 14
ER  - 
TY  - JOUR
A1  - Groh, Janos
A1  - Abdelwahab, Tassnim
A1  - Kattimani, Yogita
A1  - Hörner, Michaela
A1  - Loserth, Silke
A1  - Gudi, Viktoria
A1  - Adalbert, Robert
A1  - Imdahl, Fabian
A1  - Saliba, Antoine-Emmanuel
A1  - Coleman, Michael
A1  - Stangel, Martin
A1  - Simons, Mikael
A1  - Martini, Rudolf
T1  - Microglia-mediated demyelination protects against CD8\(^+\) T cell-driven axon degeneration in mice carrying PLP defects
JF  - Nature Communications
N2  - Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes. We show that persistent ensheathment with perturbed myelin poses a risk for axon degeneration, neuron loss, and behavioral decline. We demonstrate that CD8\(^+\) T cell-driven axonal damage is less likely to progress towards degeneration when axons are efficiently demyelinated by activated microglia. Mechanistically, we show that cytotoxic T cell effector molecules induce cytoskeletal alterations within myelinating glia and aberrant actomyosin constriction of axons at paranodal domains. Our study identifies detrimental axon-glia-immune interactions which promote neurodegeneration and possible therapeutic targets for disorders associated with myelin defects and neuroinflammation.
KW  - diseases of the nervous system
KW  - myelin biology and repair
KW  - neuroimmunology
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357641
VL  - 14
ER  -