Date of Award
Master of Science
Neural stem cells (NSCs) have received recent attention due to their potential use in transplantation therapy for a number of neurological diseases. The Alzheimer's Disease (AD) brain is a uniquely challenging environment for transplanted cells due to the presence of amyloid-beta (A[beta]) peptide, which is known to be toxic to neurons. The effects of A[beta] on NSCs have just recently begun to be investigated. Here, we examine the effect of A[beta] 25-35 on hippocampal progenitor cells (HPCs) from embryonic and adult rat. We also examine the effect of the tripeptide Gly-Pro-Arg (GPR) which has been reported to rescue primary culture neurons from A[beta]-induced toxicity. HPCs exposed to A[beta] in culture showed decreased viability as measured by MTT mitochondrial dehydrogenase assay; GPR was not protective against A[beta]-induced viability loss. A[beta] affected differentiation of adult, but not embryonic HPCs; adult HPCs exposed to A[beta] expressed the neural stem cell marker Nestin at higher levels than did controls. A[beta] did not affect proliferation of embryonic HPCs, although GPR did suppress embryonic HPC proliferation. A[beta] also did not show differential effects on proliferating neurons or glia, as determined by colabeling of BrdU and the neuronal marker MAP2 or the astrocytic marker GFAP. Our findings suggest that A[beta] decreases viability and affects differentiation of neural progenitor cells; however, specific effects upon neurogenesis or NPC proliferation were not seen.
James Noel Eucher
Eucher, James Noel, "Amyloid-beta peptide affects viability and differentiation of embryonic and adult rat hippocampal progenitor cells" (2004). Retrospective Theses and Dissertations. 17517.