Dysregulation of Glutamatergic Neurotransmission in Autism Spectrum Disorders

Despite the great number of observations being made concerning cellular and molecular dysfunctions associated with autism spectrum disorders (ASD), an integrative and unifying mechanism to explain the heterogeneous symptoms and etiology of ASD has not been proposed in the major scientific literature. We offer the explanation of potential etiology of ASD as dysregulation of glutamatergic neurotransmission with underlying interactions between chronic microglial activation and the excitotoxic cascade playing the central role. This chapter summarizes current knowledge of the structural and functional diversity of glutamate receptors (GluRs) and excitatory amino acid transporters. Recent research of the autism genome also supports the view that abnormalities in genes connected with glutamate neurotransmission and disturbed regulation of glutamate pathways may be directly involved in ASD. We further suggest that the increasing prevalence of ASD during the last decades might reflect the synergistic action of an increased burden of new excitotoxic factors. In this chapter we discuss the effects of dietary excitatory amino acids, mainly glutamate and aspartate, which could exacerbate the pathological and clinical symptoms of ASD. The mechanism of excitotoxicity is the topic of the next chapter.