Contributions
Abstract: P1754
Type: Poster Sessions
Abstract Category: N/A
Neurodegeneration in the central nervous system (CNS) as one of the histopathological hallmarks of Multiple Sclerosis (MS) is tightly associated with clinical disability and disease progression. A large body of evidence points to the central role of microglial cells in these degenerative processes. However, the exact underlying mechanisms which drive this cell population towards a deleterious phenotype are still largely elusive. In previous studies we demonstrated that via its envelope protein Env human endogenous retrovirus type W (pHERV-W) interferes with oligodendroglial precursor cell (OPC) differentiation thereby inhibiting remyelination. Here, we now investigated how Env contributes to axonal injury in MS. We could demonstrate that Env-positive microglia are abundantly present in MS lesions adjacent to sites of axonal injury. Env-mediated activation of microglia leads to a change to ameboid cell morphology, an increased cell proliferation, an induction and excretion of proinflammatory agents, a reduced expression of neuroprotective factors and a diminished myelin clearance capacity. In addition, in Env-stimulated neuron-microglia cocultures microglia can be found in tight association with compromised axons. These findings suggest that Env-mediated modulation of microglial homeostasis fuels and contributes to axonal damage in MS promoting neurodegeneration.
Disclosure: David Kremer: nothing to disclose
Joel Gruchot: nothing to disclose
Vivien Weyers: nothing to disclose
Lisa Oldemeier: nothing to disclose
Peter Göttle: nothing to disclose
Luke Healy: nothing to disclose
Jeong Ho Jang: nothing to disclose
Ranjan Dutta: nothing to disclose
Bruce Trapp: nothing to disclose
Hervé Perron: nothing to disclose
Hans-Peter Hartung: nothing to disclose
Patrick Küry: nothing to disclose
Abstract: P1754
Type: Poster Sessions
Abstract Category: N/A
Neurodegeneration in the central nervous system (CNS) as one of the histopathological hallmarks of Multiple Sclerosis (MS) is tightly associated with clinical disability and disease progression. A large body of evidence points to the central role of microglial cells in these degenerative processes. However, the exact underlying mechanisms which drive this cell population towards a deleterious phenotype are still largely elusive. In previous studies we demonstrated that via its envelope protein Env human endogenous retrovirus type W (pHERV-W) interferes with oligodendroglial precursor cell (OPC) differentiation thereby inhibiting remyelination. Here, we now investigated how Env contributes to axonal injury in MS. We could demonstrate that Env-positive microglia are abundantly present in MS lesions adjacent to sites of axonal injury. Env-mediated activation of microglia leads to a change to ameboid cell morphology, an increased cell proliferation, an induction and excretion of proinflammatory agents, a reduced expression of neuroprotective factors and a diminished myelin clearance capacity. In addition, in Env-stimulated neuron-microglia cocultures microglia can be found in tight association with compromised axons. These findings suggest that Env-mediated modulation of microglial homeostasis fuels and contributes to axonal damage in MS promoting neurodegeneration.
Disclosure: David Kremer: nothing to disclose
Joel Gruchot: nothing to disclose
Vivien Weyers: nothing to disclose
Lisa Oldemeier: nothing to disclose
Peter Göttle: nothing to disclose
Luke Healy: nothing to disclose
Jeong Ho Jang: nothing to disclose
Ranjan Dutta: nothing to disclose
Bruce Trapp: nothing to disclose
Hervé Perron: nothing to disclose
Hans-Peter Hartung: nothing to disclose
Patrick Küry: nothing to disclose