Autism is a severe neurodevelopmental disorder with genetic and environmental etiologies and a prevalence rate of 16 per 10,000, which appears to result from altered development of nervous tissue pre- and postnatally. The central hypothesis of this application is that certain gene families involved in cell growth and migration and GABAergic neurotransmission will be altered in autism. This central hypothesis will be tested and the objectives of this application accomplished by pursuing two Specific Aims: 1) Determine the mRNA and protein levels for Reelin, its receptors, and downstream molecules in the Reelin signaling system in cerebellar, hippocampal, and frontal cortices of autistic subjects and matched controls;and 2) Determine the mRNA and protein levels for GAD 65 and 67 kDa proteins and GABA receptors in cerebellar, hippocampal, and frontal cortices of autistic subjects and matched controls. We will employ previously established qRTPCR, SDS-PAGE and western blotting, and in situ hybridization techniques to quantify various mRNA and protein species. It is our expectation that we will demonstrate gene and protein alterations in brains of autistics involving GABAergic markers, Reelin and its downstream components, linking GABAergic dysfunction to autistic brain structural abnormalities. Such outcomes will be significant, because they are expected to identify biochemical mechanisms responsible for abnormal brain development in early childhood, as seen in autism.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-BDCN-N (90))
Program Officer
Kau, Alice S
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University of Minnesota Twin Cities
Schools of Medicine
United States
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Folsom, Timothy D; Thuras, Paul D; Fatemi, S Hossein (2015) Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders. Schizophr Res 165:201-11
Fatemi, S Hossein; Folsom, Timothy D (2015) GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism. Schizophr Res 167:42-56
Fatemi, S Hossein; Folsom, Timothy D (2014) Existence of monomer and dimer forms of mGluR5, under reducing conditions in studies of postmortem brain in various psychiatric disorders. Schizophr Res 158:270-1
Fatemi, S Hossein; Reutiman, Teri J; Folsom, Timothy D et al. (2014) Downregulation of GABAA receptor protein subunits ?6, ?2, ?, ?, ?2, ?, and ?2 in superior frontal cortex of subjects with autism. J Autism Dev Disord 44:1833-45
Fatemi, S Hossein (2013) Cerebellum and autism. Cerebellum 12:778-9
Folsom, Timothy D; Fatemi, S Hossein (2013) The involvement of Reelin in neurodevelopmental disorders. Neuropharmacology 68:122-35
Fatemi, S Hossein; Aldinger, Kimberly A; Ashwood, Paul et al. (2012) Consensus paper: pathological role of the cerebellum in autism. Cerebellum 11:777-807
Blatt, Gene J; Fatemi, S Hossein (2011) Alterations in GABAergic biomarkers in the autism brain: research findings and clinical implications. Anat Rec (Hoboken) 294:1646-52
Fatemi, S Hossein; Folsom, Timothy D (2011) The role of fragile X mental retardation protein in major mental disorders. Neuropharmacology 60:1221-6
Fatemi, S Hossein (2011) Reelin, a marker of stress resilience in depression and psychosis. Neuropsychopharmacology 36:2371-2

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