Figure 1.
Serotonergic innervation and neurochemical levels of 5-HT and 5-HIAA in the forebrain of BDNF+/− or WT mice. Darkfield photomicrographs (A–D) of 5-HT-immunoreactive axons (sagittal sections) in WT (A and C) and BDNF+/− mice (B and D) at 3 months (A and B) or 18 months (C and D) of age. There is a normal 5-HT axon density in neocortex and hippocampus of younger BDNF+/− mice but a loss of axons in 18-month-old BDNF+/− mice relative to WT mice of the same age; we also observed a loss of 5-HT axon density in some of the 12-month-old BDNF+/− mice relative to age-matched WT controls (not shown). The total tissue contents of 5-HT (E) and its metabolite 5-HIAA (F) in the neocortex, hippocampus, and hypothalamus of BDNF+/− and WT littermates at 3, 12, or 18 months of age were measured by HPLC (n = 6–9/group). Data is expressed as a percentage of the mean value found in age-matched WT controls. Repeated measures ANOVA revealed significant reductions in the levels of 5-HT (F1,16 = 7.42, P < 0.05) and 5-HIAA (F1,16 = 8.04, P < 0.05) in 18-month-old BDNF+/− mice relative to WT littermates but not in the younger mutant mice (P > 0.05) in these brain areas. *, P < 0.05.