Contributions
Abstract: P1200
Type: Poster
Abstract Category: Therapy - disease modifying - Neuroprotection
Background: It was recently observed that T-cell mediated neuroprotection after CNS injury can be assigned to the direct action of Interleukin-4 (IL-4) on neurons. In order to study this phenomenon in detail and on a more human- and Multiple Sclerosis (MS)-specific context, we used human primary neurons (hPNs) generated from MS patients" renal cells via an induced pluripotent stem cell (iPSC) method. These hPNs, carrying all the genetic characteristics of MS patients, were analysed for cell survival and their regenerative behaviour after injury in the presence of IL-4.
Obejctive: This study focuses on the direct effect of IL-4 on human MS patient-specific neurons under oxidative stress and axonal transection conditions, characteristic cellular stressors in the context of MS.
Methods: MS patient-derived hPNs were used for an apoptosis assay with H2O2 acting as the cellular stressor, mimicking inflammatory conditions. Cells were also used for analysing axonal regrowth and calculating a general growth potential after axotomy. Experiments were done in the presence of IL-4 in comparison to control. Additionally, the potential effect of IL-4 on axonal mitochondrial transport was assessed.
Results: hPNs treated with 25 µm H2O2 for 24 hours resulted in a high apoptosis rate, which was significantly reduced by the addition of 250 pg/ml IL-4. However, while IL-4 treatment did not significantly alter the axonal regrowth and growth potential of hPNs after mechanical axonal transection, 24-hours IL-4 pre-treatment slightly enhanced growth response following injury. Finally, one hour of IL-4 exposure to unstressed hPNs resulted in a significant decrease in average retrograde mitochondrial speed as compared to cells not exposed to IL-4.
Conclusion: These results demonstrate a highly relevant neuroprotective effect of IL-4 in the context of oxidative stress in a human MS disease-in-a-dish model, though its effect on axonal transection remains to be elucidated. Furthermore, the observed retrograde mitochondrial velocity alteration demonstrates the potential of IL-4 in modulating important metabolic functions in MS derived neurons.
Disclosure:
Sarah Hirschberg: nothing to disclose
Barbara Gisevius: nothing to disclose
Megan G. Massa: nothing to disclose
Nina Schneiders: nothing to disclose
Ralf Gold: has received payments for consultancy from Biogen and Teva; speaker honoraria and research grants from Biogen Idec Germany, Teva, Sanofi Aventis, Novartis, Bayer Healthcare and Merck Serono.
Aiden Haghikia: has received limited travel grants from Bayer Healthcare and Genzyme, and limited research grants from Genzyme.
Abstract: P1200
Type: Poster
Abstract Category: Therapy - disease modifying - Neuroprotection
Background: It was recently observed that T-cell mediated neuroprotection after CNS injury can be assigned to the direct action of Interleukin-4 (IL-4) on neurons. In order to study this phenomenon in detail and on a more human- and Multiple Sclerosis (MS)-specific context, we used human primary neurons (hPNs) generated from MS patients" renal cells via an induced pluripotent stem cell (iPSC) method. These hPNs, carrying all the genetic characteristics of MS patients, were analysed for cell survival and their regenerative behaviour after injury in the presence of IL-4.
Obejctive: This study focuses on the direct effect of IL-4 on human MS patient-specific neurons under oxidative stress and axonal transection conditions, characteristic cellular stressors in the context of MS.
Methods: MS patient-derived hPNs were used for an apoptosis assay with H2O2 acting as the cellular stressor, mimicking inflammatory conditions. Cells were also used for analysing axonal regrowth and calculating a general growth potential after axotomy. Experiments were done in the presence of IL-4 in comparison to control. Additionally, the potential effect of IL-4 on axonal mitochondrial transport was assessed.
Results: hPNs treated with 25 µm H2O2 for 24 hours resulted in a high apoptosis rate, which was significantly reduced by the addition of 250 pg/ml IL-4. However, while IL-4 treatment did not significantly alter the axonal regrowth and growth potential of hPNs after mechanical axonal transection, 24-hours IL-4 pre-treatment slightly enhanced growth response following injury. Finally, one hour of IL-4 exposure to unstressed hPNs resulted in a significant decrease in average retrograde mitochondrial speed as compared to cells not exposed to IL-4.
Conclusion: These results demonstrate a highly relevant neuroprotective effect of IL-4 in the context of oxidative stress in a human MS disease-in-a-dish model, though its effect on axonal transection remains to be elucidated. Furthermore, the observed retrograde mitochondrial velocity alteration demonstrates the potential of IL-4 in modulating important metabolic functions in MS derived neurons.
Disclosure:
Sarah Hirschberg: nothing to disclose
Barbara Gisevius: nothing to disclose
Megan G. Massa: nothing to disclose
Nina Schneiders: nothing to disclose
Ralf Gold: has received payments for consultancy from Biogen and Teva; speaker honoraria and research grants from Biogen Idec Germany, Teva, Sanofi Aventis, Novartis, Bayer Healthcare and Merck Serono.
Aiden Haghikia: has received limited travel grants from Bayer Healthcare and Genzyme, and limited research grants from Genzyme.