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Fig. 3. Changes in sAPP concentration modify the number of SVZ progenitors through
regulation of their proliferation. (A-D) Mice were intraventricularly infused
with human IgG (control), sAPP-Fc (sAPP), 0.09% NaCl (saline), batimastat
(bat), batimastat and sAPP (bat+sAPP), sense or antisense APP oligonucleotides
(S, AS). In A and C, NS were prepared from the SVZ ipsilateral to the side of
infusion and counted. In B and D, BrdU was injected 1 hour before sacrifice
and the percentage of BrdU-positive EGFR immunoreactive cells on the side of
infusion was counted. Results are shown as mean±s.e.m. of six infused
mice. (A,B) Augmentation of sAPP concentration leads to an increased number of
EGF-responsive NS progenitors in the SVZ (A) and to their increased
proliferation (B). (C) Reduction of sAPP secretion by batimastat or of APP
synthesis by antisense oligonucleotides decreases the number of EGF-responsive
NS progenitors. (Bottom panel) APP immunoblotting of the SVZ from two sense
(S) or two antisense (AS) oligonucleotide-infused mice reveals a 30% reduction
in APP levels in AS. (D) Reduction of APP synthesis through antisense
oligonucleotide infusion downregulates EGFR immunoreactive cell proliferation
and sAPP compensates this downregulation. (E) Ara-C infusion was followed by a
3 day intraventricular infusion of control IgG (Ara-C and IgG) or 6 E10
antibody (Ara-C and 6 E10) and the total number of BrdU-positive cells was
counted in whole-mount preparations of the anterior SVZ. During SVZ
regeneration, reduction of circulating sAPP downregulates EGF-responsive cell
proliferation.
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