METHODS: In the current study we have investigated expression of four targets of FMRP and mGluR5 signaling -
homer 1,
amyloid beta A4 precursor
protein (APP),
ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched
protein tyrosine phosphatase (STEP) - in the cerebellar vermis and superior frontal cortex (BA9) via SDS-PAGE and western blotting. Data were analyzed based on stratification with respect to age (children and adolescents vs. adults), anatomic region of the brain (BA9 vs. cerebellar vermis), and impact of medications (children and adolescents on medications (n = 4) vs. total children and adolescents (n = 12); adults on medications (n = 6) vs. total adults (n = 12)).
RESULTS: There were significant increases in RAC1, APP 120 kDa and APP 80 kDa
proteins in BA9 of children with
autism vs. healthy controls. None of the same
proteins were significantly affected in cerebellar vermis of children with
autism. In BA9 of adults with
autism there were significant increases in RAC1 and STEP 46 kDa and a significant decrease in
homer 1 vs. controls. In the vermis of adult subjects with
autism, RAC1 was significantly increased while APP 120, STEP 66 kDa, STEP 27 kDa, and
homer 1 were significantly decreased when compared with healthy controls. No changes were observed in vermis of children with
autism. There was a significant effect of
anticonvulsant use on STEP 46 kDa/β-actin and a potential effect on
homer 1/NSE, in BA9 of adults with
autism. However, no other significant confound effects were observed in this study.
CONCLUSIONS: Our findings provide further evidence of abnormalities in FMRP and mGluR5 signaling partners in brains of individuals with
autism and open the door to potential targeted treatments which could help ameliorate the symptoms of
autism.