the cyclic amp cascade is altered in the fragile x nervous system环腺苷酸级联是脆性x改变神经系统.pdfVIP

The Cyclic AMP Cascade Is Altered in the Fragile X Nervous System 1,2,3 1 3,5 4 5 6 Daniel J. Kelley , Richard J. Davidson , Jamie L. Elliott , Garet P. Lahvis , Jerry C. P. Yin , Anita Bhattacharyya * 1 Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin, Madison, Wisconsin, United States of America, 2 Neuroscience Training Program, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America, 3 Medical Scientist Training Program, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, United States of America, 4 Department of Surgery, University of Wisconsin, Madison, Wisconsin, United States of America, 5 Department of Genetics, University of Wisconsin, Madison, Wisconsin, United States of America, 6 Stem Cells and Developmental Disorders Laboratory, Waisman Center, University of Wisconsin, Madison, Wisconsin, United States of America Fragile X syndrome (FX), the most common heritable cause of mental retardation and autism, is a developmental disorder characterized by physical, cognitive, and behavioral deficits. FX results from a trinucleotide expansion mutation in the fmr1 gene that reduces levels of fragile X mental retardation protein (FMRP). Although research efforts have focused on FMRP’s impact on mGluR signaling, how the loss of FMRP leads to the individual symptoms of FX is not known. Previous studies on human FX blood cells revealed alterations in the cyclic adenosine 39, 5 9-monophosphate (cAMP) cascade. We tested the hypothesis that cAMP signaling is altered in the FX nervous system using three different model systems. Induced levels of cAMP in pla