Investigation of Transplanted Neural Stem Cells : The Extent of their Abil i ty to Improve Cognitive Deficit in Response to an Induced Lesion

F a c u l t y M e n t o r Jasmin Tanaja, recognizing the importance of advancements in stem cell research, began work on her own project in Professor LaFerla’s lab. Her study is the first to show that stem cells can help improve cognitive performance after a focal brain lesion targeted specifically to a neuronal subpopulation. She describes her research experience to be one of “uncovering another mystery of science,” and feels fortunate to have been a part of its discovery. Jasmin followed this research by beginning a new clinical research project on emergency medicine at the UCI Medical Center. She hopes to follow her years at UCI by moving on to graduate school. N and synaptic losses are prominent in most clinical conditions. Many experiments have used site-specific lesioning methods to mimic such conditions. These approaches may cause non-specific damage, affect multiple cell types, or cause loss of cells. To study the effect of a targeted neuronal lesion, we generated a novel transgenic mouse model in which it is possible to ablate specific types of neurons by a system of induction. This approach takes advantage of the tet-off system to drive the expression of diphtheria toxin A-chain (DTA), which relies mainly on the presence or absence of a tetracycline analog—in our case doxycycline—to deactivate or activate the expression of DTA respectively. Post induction, neural stem cells (NSC) were transplanted in the hippocampal region of the mice. After histological and behavioral assessment, we found that the neural stem cells were multipotent, and differentiated into astrocytes and oligodendrocyte precursors, although a smaller number differentiated into neurons. Analysis indicated percentages of differentiation as follows: 1.78% ± 0.515 neurons, 15.39% ± 6.76 astrocytes, and 17.07% ± 3.49 oligodendrocyte precursors. Behaviorally, the NSC-transplanted-mice performed significantly better than the controls in hippocampal-dependent tests. These transplanted neural stem cells show therapeutic potential to improve cognitive deficit.