GM-CSF treatment in AD mice reduced brain amyloidosis, increased plasma Aβ, and rescued cognitive impairment with increased hippocampal expression of calbindin and synaptophysin and increased levels of doublecortin-positive cells in the dentate gyrus.
The expression of neural stem cells (NSCs) (nestin) and neural precursors such as doublecortin (DCX) and GFAP in AD mice were decreased with age, as well as there being a reduction in 5-bromo-2-deoxyuridine (BrdU)-positive cells, when compared to WT.
In our longitudinal study with AD model mice (5XFAD mice), we found that the number of doublecortin (neurogenesis marker)-positive cells in 5XFAD mice was significantly decreased compared to wild-type littermate mice.
Translation of these effects in vivo was assessed in wild type and AD APPswe transgenic (Tg2576) mice by doublecortin (DCX) immunohistochemical analysis of neurogenesis in the SVZ, which was significantly elevated by 16 day systemic (+)-phenserine treatment, in the presence of a (+)-phenserine-induced elevation in brain- derived neurotrophic factor (BDNF).