RdU+/Prox1, respectively) or glial lineages followingVeeraraghavalu et 1-Oleoyl lysophosphatidic acid al. Molecular Neurodegeneration > 자유게시판

RdU+/Prox1, respectively) or glial lineages followingVeeraraghavalu et al. Molecular Neurodegeneration 2013, 8:41 http://www.molecularneurodegeneration.com/content/8/1/Page 6 ofFigure 4 Microglia conditioned media from PS1 M146V KI mice impairs proliferation of AHNPCs. Representative image eGFP+ microglia (green) with ramified process in DG of PS1M146V/+ x Cx3Cr1GFP/+ mice (A) and are negative for astrocytic marker, GFAP PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/11011031 (red) (B). Bright field (C) and fluorescent (D) images of flow cytometry sorted primary eGFP+ cultures established from neonatal brains of PS1M146V/+ x Cx3Cr1GFP/+ mice. Scale bar, 25 m. Bright field image of AHNPCs grown as neurospheres from PS1+/+, mice (E). Scale bar, 50 m. (F) Proliferation achieved by PS1+/+ AHNPCs following treatment with CM collected from IL-4 activated or PS1+/+ x Cx3Cr1GFP/+ or PS1M146V/+ x Cx3Cr1GFP/+ microglia. Graph shows the extent of BrdU uptake in AHNPCs observed on days 1, 3 and 6. T-test; N = 3 independent cultures, with quadruplicates for each time point (m ?SEM). ** p < 0.01.EE. Instead, we observed a prominent reduction in the percentage of new born progenitors that differentiated towards mature neuronal NeuN+ and NeuroD1+ lineages in PS1M146V/+ and PS1M146V/M146V mice. The lack of obvious changes in immature neuronal lineages correlates with the observations reported earlier in FADlinked PSEN1P264L KI mice [28]. Consistent with the reduction in the number of new born neurons generated under EE conditions, the numbers of BrdU+ cells that survive two weeks post labeling were also diminished in PS1M146V/+ and PS1M146V/M146V mice. It should be noted that we chose a two week time point for these latter analysis in order to score neuronal or glial lineage commitment of AHNPCs and their survival efficiency. The limitation of this analysis is that cells expressing mature neuronal markers may not be functionally integrated into the hippocampal network. It is presently unclear whether the reduction in AHNPC proliferation and mature neuronal differentiation in PS1M146V/+ and PS1M146V/M146V mice are a reflection of reductions in PS1 "activity", but earlier studies by Wang and colleagues offer an important insight [29]. In the latter studies, AHNPC proliferation in standard housed PS1M146V/- mice, wherein the mutant allele was placed in a PSEN1 KO background, exhibited significant reductions in both proliferation and neurogenic potential of AHNPC compared with PS1M146V/+ mice [29]. The authors concluded that wild-type PSmay play a "protective" role over the effects of the mutant M146V variant. While the nature of the PS1dependent "activity" remains to be ascertained, our demonstration that lowering the levels of wild-type PS1 leads to reduced AHNPC proliferation and neuronal differentiation studies, taken together with the findings reported by Wang and colleagues [29], would be consistent with the idea that mutant PS1 exhibits a partial "loss of function", as has been proposed earlier [30]. Third, we report that the survival of BrdU-labeled AHNPCs from PS1M146V/+ and PS1M146V/M146V mice exposed to EE were significantly reduced compared with PS1+/+mice. While the molecular mechanism(s) underlying this aspect of mutant PS1 function is presently unclear, evidence from several earlier studies have accrued that support our observations [31-33]. For example, Guo et al. [14] reported that hippocampal neurons in PS1M146V/M146V mice exhibit enhanced susceptibility to kianate-induced necrosis and that pri.