The influence of calcium signaling on the development of autism spectrum disorders

Abstract

Autism spectrum disorders (ASDs) are a group of neuropsychiatric diseases with a complex etiopathogenesis. Neuronal disorders leading to autistic symptoms are determined by dysfunction of signaling pathways. Recent studies have demonstrated that the calcium signaling pathway is one of the major significant pathways for this group of disorders. Calcium signaling is closely linked to MAPK–, Wnt–, and PI3K/AKT/mTOR -pathways, which abnormalities lead to dysfunction of serotonergic, dopaminergic, opioidergic, cholinergic, glutamatergic, and GABAergic transmission and result in excitotoxicity due to hyperactivation of NMDA and AMPA receptors and neuronal damage and death. These processes in neuronal cells are associated with formation of long-term potentiation and depression, and disturbances in these cells lead to failure of basic mental processes. From a clinical point of view, the calcium signaling pathway can become one of major targets for the pharmacological treatment of symptomatic ASD. Obviously, further animal studies and electrophysiological human studies are required for understanding pathogenetic mechanisms of ASD and the contribution of Ca²⁺ signaling. Future research will clarify a potential role of Ca²⁺ signaling in social or stereotypic behavior, which constitutes a main feature of ADS.