Figure 5.

VEGFR-1 deficiency leads to an increased generation of new neurons in the OB resulting in increased OB size. a, Schematic drawing of the migration of NPCs into the olfactory bulb. Cells entering the OB detach from the chains and mainly migrate into the inner GCL. A small percentage migrates through the PL (dark gray) into the periglomerular layer (light gray). b–f, Flt-1TK^−/− and WT mice were injected with BrdU on 5 consecutive days, and BrdU-labeled cells were analyzed on the last day of BrdU application (Day 0), after 6 (Day 6), and 30 additional days (Day 30). b, The GCL of Flt-1TK^−/− mice showed higher numbers of BrdU⁺ cells than the GCL of control animals, but this difference did not reach statistical significance. n = 5. c, In Flt-1TK^−/− mice, a significantly higher number of BrdU-labeled cells migrate through the PL. *p < 0.05; **p = 0.006; ***p < 0.0002. d, The wave of BrdU reached the PGL at day 30. Then the number of BrdU⁺ cells has more than doubled in the PGL of Flt-1TK^−/− than in WT mice. *p = 0.017; n = 5. e, Volumetric analysis of the OB revealed that Flt-1TK^−/− mice had an increased volume of the OB. The volume of every layer was significantly higher than in control animals. The PGL showed the highest increase with 157.02% of the PGL volume in controls. Total, *p = 0.0008; GCL, *p = 0.045; PGL, *p = 0.0003; PL, *p = 0.018. n = 12. f, Confocal analysis of triple immunofluorescence using the markers anti-BrdU, NeuN, and anti-tyrosine hydroxylase revealed a significant increase in the number of newly formed neurons marked by NeuN in the PGL of Flt-1TK^−/− compared with WT mice. In addition, the number of cells expressing tyrosine hydroxylase (TH), a marker of dopaminergic neurons, was significantly higher in the PGL of Flt-1TK^−/− than in controls. *p = 0.02; **p = 0.047; ***p = 0.014. Flt-1TK^−/−, n = 5; WT, n = 4.