Page 6 - ABSTRACTS ISNI

1 7t h ISNI Annual Conf erence 1042 Oral Dysfunctional brain stem cells in Alzheimer`s disease mice Tamir Ben-Hur, Nina Fainstein Neurology, Hadassah - Hebrew University Medical Center, Israel Background: Neural precursor cells (NPCs) possess powerful therapeutic immune-regulatory and neurotrophic properties. Resident brain NPCs were implicated in maintaining homeostasis in brain microenvironment. We hypothesized that in Alzheimer`s disease resident brain NPCs may be dysfunctional and fail to provide sufficient tissue support. We therefore examined functional properties of resident NPCs in young (2 months) and ageing (7 months) brains of 5xFAD mice as compared to wild type mice in-vitro and in-vivo. Methods: Freshly isolated sub-ventricular zone (SVZ) cells were examined in-vitro for their growth properties, neurotrophic effect on PC12 neurite extension, and immunomodultory effect on T cell proliferation. SVZ-NPC functions were examined in-vivo for their proliferative response to 1 week ICV Cytosine-arabinoside (AraC) infusion and their migratory response towards a lysolecithine- induced lesion in the corpus callosum (CC). Results: 5xFAD mice showed no amyloid deposition or neuronal loss at 2 months, marked amyloid deposition without neuronal loss at 7 months, and neuronal loss by age 1 year. No difference was detected in the expansion properties, inhibitory effect on T cell proliferation and effect on PC12 neurite extension of SVZ-NPCs from 2 months old 5xFAD versus wt mice. SVZ-NPCs from 7 months old 5xFAD mice exhibited 24% reduction in expansion of neurospheres, 22% diminished effect on PC12 neurite extension, and completely lost immune-modulatory ability. Basal turnover and migration of 7-months old SVZ-NPCs in-vivo was similar in 5xFAD and wt mice. However, following AraC ichallenge, 7 months old 5xFAD SVZ-NPCs recovered significantly slower than wt mice, indicated by 45% less SVZ Brdu-incorporating cells. Furthermore, there was 43% reduction in the migratory response of 7-months old 5xFAD SVZ-NPCs towards a Lysolecithine lesion. No difference in SVZ-NPC response to AraC insult or migratory response was detected among 2-months old 5xFAD and wt mice. Conclusion: SVZ derived NPCs exhibit age dependent functional loss. This might compromise their ability to maintain intact brain environment 6