Nuclear receptor TLX stimulates hippocampal neurogenesis and enhances learning and memory in a transgenic mouse model

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 25; pp. 9115 - 9120
• Main Authors: Murai, Kiyohito, Qu, Qiuhao, Sun, GuoQiang, Ye, Peng, Li, Wendong, Asuelime, Grace, Sun, Emily, Tsai, Guochuan E., Shi, Yanhong
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 24.06.2014; National Acad Sciences
• Subjects: Animal cognition; Animal memory; Animals; Biological Sciences; Brain; Cognition; Dentate Gyrus - cytology; Dentate Gyrus - metabolism; Gene Expression; Memory; Mice; Nestin - genetics; Nestin - metabolism; Neural stem cells; Neurogenesis; Neurons; Neurons - metabolism; Progenitor cells; Promoter Regions, Genetic; Quantification; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Cytoplasmic and Nuclear - genetics; Rodents; T tests; Transgenes; Transgenic animals; microRNAs; neural stem cells; NR2E1
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1406779111

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.