title: Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model.
abstract: The role of the nuclear receptor TLX in hippocampal neurogenesis and cognition has just begun to be explored. In this study, we generated a transgenic mouse model that expresses TLX under the control of the promoter of nestin, a neural precursor marker. Transgenic TLX expression led to mice with enlarged brains with an elongated hippocampal dentate gyrus and increased numbers of newborn neurons. Specific expression of TLX in adult hippocampal dentate gyrus via lentiviral transduction increased the numbers of BrdU(+) cells and BrdU(+)NeuN(+) neurons. Furthermore, the neural precursor-specific expression of the TLX transgene substantially rescued the neurogenic defects of TLX-null mice. Consistent with increased neurogenesis in the hippocampus, the TLX transgenic mice exhibited enhanced cognition with increased learning and memory. These results suggest a strong association between hippocampal neurogenesis and cognition, as well as significant contributions of TLX to hippocampal neurogenesis, learning, and memory.
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Murai
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and.
authors.forename: Qiuhao
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and.
authors.forename: GuoQiang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and.
authors.forename: Wendong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and.
authors.forename: Grace
authors.initials: G
authors.lastname: Asuelime
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and.
authors.forename: Emily
authors.initials: E
authors.lastname: Sun
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Harbor-UCLA Medical Center, Torrance, CA 90509.
authors.forename: Guochuan E
authors.initials: GE
authors.lastname: Tsai
authors.affiliation: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010 and yshi@coh.org.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D003071:Cognition; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D008568:Memory; D051379:Mice; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C577485:Nes protein, mouse; D064231:Nestin; C490258:Nr2e1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear
keywords: NR2E1; microRNAs; neural stem cells