Contributions
Abstract: P473
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Hallmarks of MS lesions are demyelination and axonal pathology, which occurs early after disease onset and is associated with disease progression and persistent disability in MS. Demyelination, which leads to a loss of support by oligodendrocytes, increased energy demand of the axon and/ or increased impact of toxins, is considered as the major cause for axonal damage and degeneration. The establishment of a new myelin sheath, i.e. remyelination, has been known as a mechanism of repair and axonal protection. However, the interrelation of the axon and the myelin sheath in regards of axonal damage and remyelination is unknown. Demyelination and remyelination cause a rearrangement of many transmembrane proteins, such as voltage gated potassium (KV) channels, which might result in an increased vulnerability of the axon to axonal damage due to pH shifts and ion disbalance.
To shed light onto the interrelationship of axons and the myelin sheath during de-/ and remyelination, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the density of acutely damaged and preserved axons. We observed more damaged axons in late stage demyelinated MS lesions than in late stage remyelinated MS lesions. To investigate the relation of demyelination, remyelination and axonal damage in more detail, we employed a toxic model of cuprizone-induced demyelination and performed tight time course experiments assessing the evolution of remyelination and acute axonal damage. We found neither an evidence for increased vulnerability of axons to axonal damage due to early remyelination nor that pH shifts and alteration of KV channel conductance were involved in axonal damage in the absence of an adaptive immune response.
Disclosure: V. Schultz, F. Paap, U Scheidt, A. Junker: nothing to disclose
C. Stadelmann received honoraria for speaking and travel reimbursement from Novartis Pharma GmbH, Teva Pharmaceutical Industries Ltd., Biogen, and Bayer Health Care. She served on scientific advisory boards of Novartis and Teva. She receives research support from Teva. She is a member of the editoral board of the Multiple Sclerosis Journal and Neurology: Neuroimmunology & Neuroinflammation.
W. Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. W. Brück serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.
Abstract: P473
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Repairing mechanisms
Hallmarks of MS lesions are demyelination and axonal pathology, which occurs early after disease onset and is associated with disease progression and persistent disability in MS. Demyelination, which leads to a loss of support by oligodendrocytes, increased energy demand of the axon and/ or increased impact of toxins, is considered as the major cause for axonal damage and degeneration. The establishment of a new myelin sheath, i.e. remyelination, has been known as a mechanism of repair and axonal protection. However, the interrelation of the axon and the myelin sheath in regards of axonal damage and remyelination is unknown. Demyelination and remyelination cause a rearrangement of many transmembrane proteins, such as voltage gated potassium (KV) channels, which might result in an increased vulnerability of the axon to axonal damage due to pH shifts and ion disbalance.
To shed light onto the interrelationship of axons and the myelin sheath during de-/ and remyelination, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the density of acutely damaged and preserved axons. We observed more damaged axons in late stage demyelinated MS lesions than in late stage remyelinated MS lesions. To investigate the relation of demyelination, remyelination and axonal damage in more detail, we employed a toxic model of cuprizone-induced demyelination and performed tight time course experiments assessing the evolution of remyelination and acute axonal damage. We found neither an evidence for increased vulnerability of axons to axonal damage due to early remyelination nor that pH shifts and alteration of KV channel conductance were involved in axonal damage in the absence of an adaptive immune response.
Disclosure: V. Schultz, F. Paap, U Scheidt, A. Junker: nothing to disclose
C. Stadelmann received honoraria for speaking and travel reimbursement from Novartis Pharma GmbH, Teva Pharmaceutical Industries Ltd., Biogen, and Bayer Health Care. She served on scientific advisory boards of Novartis and Teva. She receives research support from Teva. She is a member of the editoral board of the Multiple Sclerosis Journal and Neurology: Neuroimmunology & Neuroinflammation.
W. Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono, Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Novartis and Genzyme. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. W. Brück serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.