Uniform TitleEffects of erythropoietin and lithium on neural precursors and blood-derived cells
NameQu, Zhao xia (author), Grumet, Martin (chair), Young, Wise (co-chair), Hart, Ronald (internal member), Hsu, Shu-Chan (internal member), Rabson, Arnold (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionRecent studies suggest that two hematopoietic drugs, erythropoietin (EPO) and lithium, can be used to treat various central nervous system (CNS) diseases, and that neural precursor stimulation contributes to their beneficial effects on CNS diseases. We studied the effects of these two drugs on neural precursor cells and N01.1, a neonatal rat blood-derived cell clone generated in our laboratory, exhibiting some features of neural precursors.
My experimental results suggest that EPO promotes neural precursor cell growth in vitro, and may stimulate expression of EPO receptor and neural stem cell marker nestin in rat spinal cords to benefit spinal cord injury. These studies provide important insight into the physiological functions and beneficial effects of EPO in the CNS. In addition, my studies suggest that lithium promotes proliferation but not survival of neural precursors in vitro, and the mechanism does not necessarily involve neurotrophic factors, or inositol depletion, but may involve GSK-3beta inhibition and NFAT activation. These findings not only provide mechanistic insights into the clinical effects of lithium, but also suggest an alternative therapeutic strategy for bipolar disorder and other neural diseases.
EPO activated ERK pathway in N01.1 cells, which may through a c-Raf-independent mechanism. In addition, EPO tended to increase RNA levels of anti-apoptotic gene Bcl-w but not Bcl2 or Bcl-xL in N01.1 cells. These results suggest that EPO may promote N01.1 cell survival or proliferation through a mechanism different from that in erythroid precursor cells.
Lithium significantly promoted cell number increase and stimulated neurotrophic factor RNA expression in N01.1 cell cultures. In addition, lithium treatment of rats that had N01.1 cells transplanted into their injured spinal cords robustly increased N01.1 cell numbers and remarkably increased RNA levels of several neurotrophic factors in the spinal cords. These results suggest a new powerful method for improving survival or proliferation of cells transplanted into the CNS, and a new method for stimulating neurotrophic factor expression in the CNS after injury.
NoteIncludes bibliographical references (p. 139-158).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.