Neurogenesis and Learning: Making Connections in Fragile X Syndrome

Newborn neurons in the adult hippocampus may help form new memories. If so, might neurogenesis play a role in neurological disorders and adult mental retardation? New research into Fragile X syndrome suggests so. This disorder is the most common form of inherited mental retardation, and is caused by a mutation that prevents production of a single gene product, Fragile X mental retardation protein (FMRP). Although most research on the protein has focused on its role in synaptic signaling, recent studies indicate that FMRP is necessary for normal neurogenesis as well. Now, in the April 24 Nature Medicine online, researchers led by Xinyu Zhao present striking evidence that FMRP’s effects on adult neurogenesis tie directly to the learning deficits seen in a mouse model of the disorder.

To demonstrate this, Zhao and colleagues bred transgenic mice in which they could selectively turn the gene off or on in adult neural stem cells. They found that when stem cells lacked FMRP but all other brain cells expressed it normally, the mice learned hippocampal-dependent tasks poorly. Conversely, when the scientists restored FMRP expression only in adult neural stem cells in a mouse line without much FMRP, hippocampal-dependent learning returned to normal. The authors also confirmed previous findings that FMRP is necessary for normal neural stem cell proliferation and differentiation. Although many questions remain, the data hint that promoting neurogenesis might have therapeutic potential for people with Fragile X syndrome. In addition, other scientists in the field note that the genetic technique itself could have broad applications for studying not only Fragile X, but other neurological conditions as well.