Abstract
Background: Fragile X syndrome is caused by loss of function of the fragile X mental retardation 1 (FMR1) gene and shares multiple phenotypes with autism. We have previously found reduced expression of the protein product of FMR1 (FMRP) in vermis of adults with autism. Methods. In the current study, we have investigated levels of FMRP in the superior frontal cortex of people with autism and matched controls using Western blot analysis. Because FMRP regulates the translation of multiple genes, we also measured protein levels for downstream molecules metabotropic glutamate receptor 5 (mGluR5) and -aminobutyric acid (GABA) A receptor 3 (GABR3), as well as glial fibrillary acidic protein (GFAP). Results: We observed significantly reduced levels of protein for FMRP in adults with autism, significantly increased levels of protein for mGluR5 in children with autism and significantly increased levels of GFAP in adults and children with autism. We found no change in expression of GABR3. Our results for FMRP, mGluR5 and GFAP confirm our previous work in the cerebellar vermis of people with autism. Conclusion: These changes may be responsible for cognitive deficits and seizure disorder in people with autism.
| Original language | English (US) |
|---|---|
| Article number | 6 |
| Journal | Molecular Autism |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2011 |
Bibliographical note
Funding Information:Human tissue was obtained from the National Institute of Child Health & Human Development (NICHD) Brain and Tissue Bank for Developmental Disorders, University of Maryland, Baltimore, MD, USA. (The role of the NICHD Brain and Tissue Bank is to distribute tissue, and therefore it cannot endorse the studies performed or the interpretation of results.). Human tissue was also obtained from the Harvard Brain Tissue Resource Center, which is supported in part by Public Health Service R24 MH068855; the Brain Endowment Bank, which is funded in part by the National Parkinson Foundation, Inc., Miami, FL, USA; and the Autism Tissue Program, and all are gratefully acknowledged. Grant support by NICHD grants 5R01HD052074-01A2 and 3R01HD052074-03S1 to SHF is gratefully acknowledged. The funding body had no role in the study design, collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Information regarding FMRP from Dr J Darnell, Rockefeller University, New York, NY, USA, is greatly appreciated. Assistance with statistical analyses provided by Dr P Thuras is greatly appreciated. A brief summary of some of the findings presented here dealing with FMRP, mGluR5 and GABRb3 were previously presented in a review article [61] with permission from Elsevier.
Funding Information:
All experimental procedures were approved by the Institutional Review Board of the University of Minnesota School of Medicine. Postmortem blocks of superior frontal cortex (that is, BA9) were obtained from the National Institute of Child Health & Human Development Brain and Tissue Bank for Developmental Disorders, University of Maryland, Baltimore, MD, USA; the Harvard Brain Tissue Resource Center, which is supported in part by Public Health Service grant R24 MH068855; the Brain Endowment Bank, which is funded in part by the National Parkinson Foundation, Inc., Miami, FL, USA; and the Autism Tissue Program. The tissue samples (Table 1) were prepared as described previously [25-28]. Sample B6184 was tested for FXS, and the test results were negative. There are no records to indicate that any of the other individuals received genetic testing for, or were diagnosed with, FXS, duplication at chromosome 15q or any other relevant genetic abnormalities that could contribute to the pathology of autism.