Reduced rate of neural differentiation in the dentate gyrus of adult dysbindin null (sandy) mouse.

Genetic variations in the gene encoding dysbindin has consistently been associated with schizophrenia and bipolar disorder, although little is known about the neural functions carried out by dysbindin. To gain some insight into this area, we took advantage of the readily available dysbindin-null mouse sandy (sdy-/-) and studied hippocampal neurogenesis using thymidine analogue bromodeoxuridine (BrdU). No significant differences were found in the proliferation (4 hours) or survival (1, 4 and 8 weeks after the last BrdU injection) of progenitors in the subgranular regions of the dentate gyrus between sdy-/- and sdy+/+ (control) mice. However, 4 weeks after the last BrdU injection, a significant reduction was observed in the ratio of neuronal differentiation in sdy-/- when compared to that of sdy+/+ (sdy+/+  = 87.0 ± 5.3% vs. sdy-/-  = 71.3 ± 8.3%, p = 0.01). These findings suggest that dysbindin plays a role during differentiation process in the adult hippocampal neurogenesis and that its deficit may negatively affect neurogenesis-related functions such as cognition and mood.

Antitumor effect of geranylamine derivatives on human hepatoma.

In this study, we examined the antitumor activities of isoprenoid derivatives conjugated with substrates of energy metabolism in human hepatoma-bearing athymic mice. Among these compounds, N-geranylpyruvic amide, N-geranyl-p-pyruvaminobenzoic amide, N,N'-digeranylmalic diamide and N,N'-digeranyl-O-acetylmalic diamide had strong antitumor effects. These geranylamine derivatives also inhibited in vitro cell growth. Sugar conjugates of geranylamine, geranic acid and mevalonic acid did not show any antitumor effect in vivo or in vitro. Although the geranylamine derivatives had no impact on the cell cycle distribution at 24 h, a sub-G1 (apoptotic) peak of varying magnitude was seen in DNA histograms of cells treated with the derivatives for 48 h. However, the geranylamine derivatives did not inhibit protein isoprenylation, which has been reported in cancer cells treated with several natural isoprenoids. These results suggest that the geranylamine derivatives conjugated with malic acid and pyruvic acid have a different mechanism of antitumor activity from that of natural isoprenoids.