Fig. 1.

Depletion of hippocampal neurogenesis following treatment of Nestin-δ-HSV-TK and APPswePS1ΔE9/Nestin-δ-HSV-TK mice with valganciclovir. a Breeding scheme of APPswe/PS1ΔE9 and Nestin-δ-HSV-TK transgenic mice, to produce transgenic FAD animals that can exhibit selectively ablated neurogenesis, i.e. APPswePS1ΔE9/Nestin-δ-HSV-TK mice. b, c Confocal images of hippocampal sections of Nestin-δ-HSV-TK transgenic mice stained with anti-NeuN and anti-green fluorescent protein (GFP) + antibodies. Images show less GFP+ neural stem and progenitor cells in the subgranular layer of valganciclovir-treated Nestin-δ-HSV-TK mice (c) compared to vehicle-treated Nestin-δ-HSV-TK transgenic mice (b). d-f Quantification of hippocampal neurogenesis in Nestin-δ-HSV-TK that either received vehicle (black bars) or valganciclovir chow (gray bars). There was no change in the number of GFP + DCX- (d) or GFP + DCX+ cells (e), but there was a significant decrease in the number of GFP-DCX+ cells [(f) two-tailed, unpaired t-test; t ₇ = 5.589, P = 0.0008]. g, h Hippocampal sections of 4–5 month old APPswe/PS1ΔE9;Nestin-δ-HSV-TK fed with either vehicle (g) or valganciclovir (h) chow. Valganciclovir treated animals showed a significant decrease in GFP+ (nestin) and DCX+ expressing cells. i-n Quantification of hippocampal neurogenesis in APPswePS1ΔE9/Nestin-δ-HSV-TK that received vehicle- (black bar) or valganciclovir- chow (gray bar). Decrease in total number of (i) GFP + DCX- expressing neural progenitor cells (two-tailed, unpaired t-test; t ₉ = 3.253, P = 0.0099), (j) GFP + DCX+ neuroblasts (two-tailed, unpaired t-test; t ₉ = 3.305, P = 0.0092) and (k) GFP-DCX+ immature neurons (two-tailed, unpaired t-test; t ₉ = 2.932, P = 0.0167) in the subgranular layer (valganciclovir N = 5, vehicle N = 6). Counts in the granular cell layer (valganciclovir N = 4, vehicle N = 5) show decrease in number of (l) total BrdU (two-tailed, Welch’s unequal variance t-test; t _4.034 = 2.204, P = 0.0917), (m) BrdU + NeuN+ (two-tailed, Welch’s unequal variance t-test; t _4.062 = 2.077, P = 0.1054) and (n) BrdU + NeuN- (two-tailed, Welch’s unequal variance t-test; t _4.137 = 2.457, P = 0.0679). Scale bar = 100 μm. *P < 0.05; **P < 0.01