15-07-08(23:52:12)
Authors:
Bjugstad KB 1, Cornelius SK 1, Snyder EY 2, MacLean K 1
Institutions:
1. Dept. Pediatrics, Univ Colorado Denver, Aurora, CO;
2. Burnham Institute, La Jolla, CA
Title of abstract : Neural stem cells as a potential treatment for Down syndrome using young and aged trisomic Ts65Dn mice
Abstract text:
Individuals with Down syndrome (DS) are usually hit twice in their life times. First, they experience cognitive delays in young adulthood and then many face the high probability of developing Alzheimer’s disease (AD) decades before the general population. Because neural stem cells have the capacity to migrate throughout the brain, we hypothesized that neural stem cells could be used to treat DS and DS-associated AD. Using the Ts65Dn mouse model of DS, young (2 months) and aged (10 months) trisomic and disomic littermates were implanted bilaterally into the hippocampus with murine-derived neural stem cells (C17.2, mNSC). Three months post-transplant, mice underwent cognitive behavior testing. Young (now 5 months) and Aged (now 13 months) mice were tested in the conditioned taste avoidance (CTA) task in which learning is determined by the avoidance of a novel flavor. Aged mice were also tested in the Morris water maze (MWM), a task of spatial learning. At the end of behavior testing, brains were examined for preservation of host hippocampal neurons using immunohistochemistry against microtubule associated protein (MAP2). For CTA testing there were significant main effects of both karyotype and transplant, but not of age. As a group, CTA learning in the trisomic mice was improved to the level of the disomic group treated with saline. Interestingly, the disomic group treated with mNSC also improved CTA learning. In the MWM, aged trisomic mice were inconsistent in locating the escape platform compared to aged disomic littermates. Alternatively, the mNSC implanted trisomic mice consistently found the escape platform in progressively shorter times, such that by day 5 this group had shorter latencies than either disomic group. There was an age-associated loss of MAP2+ neurons in all areas of the hippocampus, however in CA3 the trisomic group had a greater loss for their age compared to disomic mice. Animals implanted with mNSC, regardless of karyotype, had greater numbers of MAP2+ neurons. Based on improved cognitive functioning and greater numbers of neurons, NSC might be a potential treatment for use in DS and DS-associated AD.
