Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism

The mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.In this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism.Autism is a pervasive developmental disorder characterized by impairments in reciprocal social interactions and communication, and the presence of repetitive and stereotyped behaviors [1]. Emerging evidence from neuroimaging studies suggests that there are abnormalities of growth, microstructure and neuronal connectivity in the brains of people with autism. For example, using magnetic resonance imaging (MRI) with a diffusion tensor imaging (DTI) technique, Barnea-Goraly et al. showed reduced fractional anisotropy (FA), which is indicative of white-matter structural alterations, in the anterior cingulate cortex (ACC) of people with autism, a region known to be related to social cognition [2]. This finding suggests that impaired structural integrity in the white matter may play an important role in the pathophysiology of autism. Because autistic symptoms begin in the first years of life and brain-growth abnormalities pr