rearing in each compartment [70]. At least 9 animals per group were investigated. Acknowledgments The authors thank Lary C. Walker (Emory University Atlanta) for helpful comments on the manuscript. References 1. Saurin W, Hofnung M, Dassa E (1999) Getting in or out: early segregation between importers and exporters in the evolution of ATP-binding cassette (ABC) transporters. J Mol Evol 48: 22–41. 2. Ferreira MJ, Sa-Nogueira I (2010) A multitask ATPase serving different ABC- type sugar importers in Bacillus subtilis. J Bacteriol 192: 5312–5318. 3. Gisin J, Muller A, Pfander Y, Leimkuhler S, Narberhaus F, et al. (2010) A Rhodobacter capsulatus member of a universal permease family imports molybdate and other oxyanions. J Bacteriol 192: 5943–5952. 4. Linton KJ (2007) Structure and function of ABC transporters. Physiology (Bethesda) 22: 122–130. 5. Hirano T (2006) At the heart of the chromosome: SMC proteins in action. Nat Rev Mol Cell Biol 7: 311–322. 6. Hopfner KP, Karcher A, Shin DS, Craig L, Arthur LM, et al. (2000) Structural biology of Rad50 ATPase: ATP-driven conformational control in DNA double- strand break repair and the ABC-ATPase superfamily. Cell 101: 789–800. 7. Kozak L, Gopal G, Yoon JH, Sauna ZE, Ambudkar SV, et al. (2002) Elf1p, a member of the ABC class of ATPases, functions as a mRNA export factor in Schizosacchromyces pombe. J Biol Chem 277: 33580–33589. 8. Dean M, Hamon Y, Chimini G (2001) The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 42: 1007–1017. 9. Dean M, Annilo T (2005) Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates. Annu Rev Genomics Hum Genet 6: 123–142. 10. Sarkadi B, Ozvegy-Laczka C, Nemet K, Varadi A (2004) ABCG2 – a transporter for all seasons. FEBS Lett 567: 116–120. 11. Pahnke J, Krohn M, Scheffler K (2009) [The role of blood-brain barrier in the pathogenesis of Alzheimer dementia–implications for immunological therapies for plaque dissolution]. Fortschr Neurol Psychiatr 77 Suppl 1: S21–24. 12. Pahnke J, Walker LC, Scheffler K, Krohn M (2009) Alzheimer’s disease and blood-brain barrier function-Why have anti-beta-amyloid therapies failed to prevent dementia progression? Neurosci Biobehav Rev 33: 1099–1108. 13. Krohn M, Lange C, Hofrichter J, Scheffler K, Stenzel J, et al. (2011) Cerebral amyloid-beta proteostasis is regulated by the membrane transport protein ABCC1 in mice. J Clin Invest 121: 3924–3931. 14. Pahnke J, Wolkenhauer O, Krohn M, Walker LC (2008) Clinico-pathologic function of cerebral ABC transporters – implications for the pathogenesis of Alzheimer’s disease. Curr Alzheimer Res 5: 396–405. 15. Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455: 152–162. 16. Kartner N, Shales M, Riordan JR, Ling V (1983) Daunorubicin-resistant Chinese hamster ovary cells expressing multidrug resistance and a cell-surface P- glycoprotein. Cancer Res 43: 4413–4419. 17. Bates SE, Robey R, Miyake K, Rao K, Ross DD, et al. (2001) The role of half- transporters in multidrug resistance. J Bioenerg Biomembr 33: 503–511. 18. Leslie EM, Deeley RG, Cole SP (2005) Multidrug resistance proteins: role of P- glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol 204: 216–237. 19. Borovski T, De Sousa EMF, Vermeulen L, Medema JP (2011) Cancer stem cell niche: the place to be. Cancer Res 71: 634–639. 20. Alison MR (2003) Tissue-based stem cells: ABC transporter proteins take centre stage. J Pathol 200: 547–550. 21. Chaudhary PM, Roninson IB (1991) Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66: 85–94. 22. Wolf NS, Kone A, Priestley GV, Bartelmez SH (1993) In vivo and in vitro characterization of long-term repopulating primitive hematopoietic cells isolated by sequential Hoechst 33342-rhodamine 123 FACS selection. Exp Hematol 21: 614–622. 23. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183: 1797–1806. 24. Lechner A, Leech CA, Abraham EJ, Nolan AL, Habener JF (2002) Nestin- positive progenitor cells derived from adult human pancreatic islets of Langerhans contain side population (SP) cells defined by expression of the ABCG2 (BCRP1) ATP-binding cassette transporter. Biochem Biophys Res Commun 293: 670–674. 25. Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, et al. (2004) The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem 279: 24218–24225. 26. Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, et al. (1997) Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug- transporting) P-glycoproteins. Proc Natl Acad Sci U S A 94: 4028–4033. ABC Transporters in Neurogenesis Author Contributions Conceived and designed the experiments: TS JP. Performed the experiments: TS JH TD KP CF AU ASP AS. Analyzed the data: TS MK. Contributed reagents/materials/analysis tools: TB CL J. Stenzel J. Steffen HJH. Wrote the paper: TS MK JP. 27. Panwala CM, Jones JC, Viney JL (1998) A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol 161: 5733–5744. 28. Jonker JW, Buitelaar M, Wagenaar E, Van Der Valk MA, Scheffer GL, et al. (2002) The breast cancer resistance protein protects against a major chlorophyll- derived dietary phototoxin and protoporphyria. Proc Natl Acad Sci U S A 99: 15649–15654. 29. Islam MO, Kanemura Y, Tajria J, Mori H, Kobayashi S, et al. (2005) Characterization of ABC transporter ABCB1 expressed in human neural stem/ progenitor cells. FEBS Lett 579: 3473–3480. 30. Islam MO, Kanemura Y, Tajria J, Mori H, Kobayashi S, et al. (2005) Functional expression of ABCG2 transporter in human neural stem/progenitor cells. Neurosci Res 52: 75–82. 31. Lin T, Islam O, Heese K (2006) ABC transporters, neural stem cells and neurogenesis – a different perspective. Cell Res 16: 857–871. 32. Kandasamy M, Couillard-Despres S, Raber KA, Stephan M, Lehner B, et al. Stem cell quiescence in the hippocampal neurogenic niche is associated with elevated transforming growth factor-beta signaling in an animal model of Huntington disease. J Neuropathol Exp Neurol 69: 717–728. 33. Steiner B, Klempin F, Wang L, Kott M, Kettenmann H, et al. (2006) Type-2 cells as link between glial and neuronal lineage in adult hippocampal neurogenesis. Glia 54: 805–814. 34. Komitova M, Mattsson B, Johansson BB, Eriksson PS (2005) Enriched environment increases neural stem/progenitor cell proliferation and neurogen- esis in the subventricular zone of stroke-lesioned adult rats. Stroke 36: 1278–1282. 35. von Bohlen Und Halbach O (2007) Immunohistological markers for staging neurogenesis in adult hippocampus. Cell Tissue Res 329: 409–420. 36. Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28: 223–250. 37. Kempermann G, Jessberger S, Steiner B, Kronenberg G (2004) Milestones of neuronal development in the adult hippocampus. Trends Neurosci 27: 447–452. 38. Kernie SG, Erwin TM, Parada LF (2001) Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 66: 317–326. 39. Yu TS, Zhang G, Liebl DJ, Kernie SG (2008) Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors. J Neurosci 28: 12901–12912. 40. Bye N, Carron S, Han X, Agyapomaa D, Ng SY, et al. (2011) Neurogenesis and glial proliferation are stimulated following diffuse traumatic brain injury in adult rats. J Neurosci Res 89: 986–1000. 41. Scheffler K, Stenzel J, Krohn M, Lange C, Hofrichter J, et al. (2011) Determination of Spatial and Temporal Distribution of Microglia by 230 nm- High-Resolution, High-Throughput Automated Analysis Reveals Different Amyloid Plaque Populations in an APP/PS1 Mouse Model of Alzheimer’s Disease. Curr Alzheimer Res 8: 781–788. 42. Manuel M, Georgala PA, Carr CB, Chanas S, Kleinjan DA, et al. (2007) Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization. Development 134: 545–555. 43. Conrad CD, Lupien SJ, Thanasoulis LC, McEwen BS (1997) The effects of type I and type II corticosteroid receptor agonists on exploratory behavior and spatial memory in the Y-maze. Brain Res 759: 76–83. 44. Holcomb L, Gordon MN, McGowan E, Yu X, Benkovic S, et al. (1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 4: 97–100. 45. Cruz AP, Frei F, Graeff FG (1994) Ethopharmacological analysis of rat behavior on the elevated plus-maze. Pharmacol Biochem Behav 49: 171–176. 46. Rodgers RJ, Dalvi A (1997) Anxiety, defence and the elevated plus-maze. Neurosci Biobehav Rev 21: 801–810. 47. Montgomery KC (1955) The relation between fear induced by novel stimulation and exploratory behavior. J Comp Physiol Psychol 48: 254–260. 48. Yamamoto A, Shofuda T, Islam MO, Nakamura Y, Yamasaki M, et al. (2009) ABCB1 is predominantly expressed in human fetal neural stem/progenitor cells at an early development stage. J Neurosci Res 87: 2615–2623. 49. Shen Q, Wang Y, Kokovay E, Lin G, Chuang SM, et al. (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3: 289–300. 50. Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, et al. (2004) Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304: 1338–1340. PLoS ONE | www.plosone.org 13 April 2012 | Volume 7 | Issue 4 | e35613