ABC Transporters in Neurogenesis Figure 10. Light/dark box experiments verified altered anxiety and exploratory behavior. Comparing the running distance of the animals in the open field revealed no significant differences (A). However, the distance traveled by ABCB1-deficient mice (+64%) in the dark compartment (B) was significantly increased compared to the controls. Also, the time in the dark compartment (C) was significantly increased in ABCB10/0 mice (+78%) compared to controls. The mean number of transitions between the two compartments (D) was impaired in both ABCB10/0 (259%) and ABCC10/ 0 (249%) mice. Comparing the rearing frequency in both compartments revealed a significant decrease for ABCC10/0 (267%) mice in the open field (E), while the frequency was increased in the dark compartment (F) for ABCB10/0 (+71%) mice. Error bar: SEM, *,p0.05; **p,0.01. doi:10.1371/journal.pone.0035613.g010 cellular homeostasis. In our experiments, the effects of ABCC1- deficiency became most evident after CCI. Interestingly, ABCC1 has been discovered recently to play an important role in the excretion of toxic Ab peptides in Alzheimer’s disease models via the brain’s barriers [13]. In addition to its accumulation in amyloid plaques, Ab monomers and oligomers have been recognized to directly impair NSPC function [53]. Since the present study shows that ABCC1 function also is important for stem cell differentiation during disease states, it appears that ABC transporters perform dual functions: i) clearing the brain of toxic metabolites, and ii) preserving the microenvironment of the stem cells in their niche. Both functions are necessary to protect against age-related neurodegenerative processes. Inasmuch as the lack of ABC transporters affects cellular function in the brain, we hypothesized that behavioral integrity might be compromised as well. Therefore, we assessed the effects of ABC transporter deficiency on specific behaviors by using the Y-maze, elevated plus-maze and light/dark box to assess overall activity, exploratory drive and anxiety. We detected marked differences in both activity and exploratory behavior in ABCB1- and ABCC1- deficient mice. The decreased activity might partially reflect the increased anxiety levels that were detected in the elevated plus maze. Notably, light/dark box tests revealed complex behavioral altera- tions in those mice. While both ABCB10/0 and ABCC10/0 mice show stronger avoidance of the light area (stress) than did controls, ABCB10/0 mice displayed reduced fear/enhanced exploratory behavior under non-stress conditions (dark area) and normal PLoS ONE | www.plosone.org 10 April 2012 | Volume 7 | Issue 4 | e35613