Our laboratory has recently obtained evidence from an in vitro synaptoneurosome preparation that the fragile X gene product, a protein termed FMRP, is translated from mRNA at locations near synapses in response to glutamatergic activation of metabotropic receptors. This finding complements other work on the fragile X gene (FMR-1) and the fragile X syndrome, a form of mental retardation correlated with the absence of normal FMRP expression, all of which suggest that FMRP may play a role in the process whereby synaptic activity during development and/or learning results in a structural and functional maturation of the synapse. We propose a series of basic studies of the rodent brain designed to further explore in vivo, 1) the spatio-temporal pattern of the expression of FMRP during development, 2) the possible correlation of FMRP expression with other major developmental processes, such as synaptogenesis, in order to explore possible reasons for the pathological effects of FMRP deficiencies on brain development, and 3) the effects of behavioral experience on FMRP expression in brain regions known to exhibit structural plasticity in response to behavioral experience manipulations, studying visual cortex in monocularly deprived animals and animals exposed to an enriched environment, and motor cortex in animals after acrobatic motor skill learning. Fragile X syndrome, which can arise from a mutation that prevents gene expression or from point mutations affecting the structure of the gene product, is one of the most common forms of inherited mental retardation known. Furthermore, it is commonly associated with autism and attention deficit hyperactivity disorder. Knowledge of the role of FMRP in synapse maturation and brain function may well give rise to treatments for these syndromes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30MH011272-06
Application #
6530809
Study Section
Molecular, Cellular, and Developmental Neurobiology Review Committee (MCDN)
Program Officer
Curvey, Mary F
Project Start
2002-02-21
Project End
Budget Start
2002-02-21
Budget End
2002-05-05
Support Year
6
Fiscal Year
2002
Total Cost
$13,387
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Organized Research Units
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Irwin, Scott A; Christmon, Chariya A; Grossman, Aaron W et al. (2005) Fragile X mental retardation protein levels increase following complex environment exposure in rat brain regions undergoing active synaptogenesis. Neurobiol Learn Mem 83:180-7
Churchill, James D; Grossman, Aaron W; Irwin, Scott A et al. (2002) A converging-methods approach to fragile X syndrome. Dev Psychobiol 40:323-38
Irwin, Scott A; Idupulapati, Madhuri; Gilbert, Molly E et al. (2002) Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am J Med Genet 111:140-6
Irwin, S A; Patel, B; Idupulapati, M et al. (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet 98:161-7
Irwin, S A; Galvez, R; Greenough, W T (2000) Dendritic spine structural anomalies in fragile-X mental retardation syndrome. Cereb Cortex 10:1038-44
Irwin, S A; Swain, R A; Christmon, C A et al. (2000) Evidence for altered Fragile-X mental retardation protein expression in response to behavioral stimulation. Neurobiol Learn Mem 74:87-93
Irwin, S A; Swain, R A; Christmon, C A et al. (2000) Evidence for altered Fragile-X mental retardation protein expression in response to behavioral stimulation. Neurobiol Learn Mem 73:87-93