Insulin‐Like Growth Factor and Insulin‐Like Growth Factor Receptor Expression in Human Idiopathic Autism Fusiform Gyrus Tissue. Issue 6 (10th March 2020) - Cioana, Milena
Abstract : Autism spectrum disorder (ASD) is believed to stem from defects in the establishment and maintenance of functional neuronal networks due to synaptic/spine dysfunction. The potent effects of IGF‐1 on synaptic function, maintenance, and plasticity make it a potential target for treating ASD. This polypeptide hormone has proven to have beneficial effects in treating related developmental disorders like Rett syndrome, and its efficacy in ASD is currently being investigated in a pilot study. IGF‐1 binds to its receptor (IGF‐1R) in neurons and activates mitogen‐activated protein kinase and PI3K/Akt signaling to produce biological effects on spine function. The PI3K/Akt pathway is dysregulated in ASD, including idiopathic autism, and is thus believed to play a role in the disorder. Despite this, no study has explored the levels of IGF‐1 in the fusiform gyrus of idiopathic autism patients, an area known to be hypoactivated in ASD, and no study has examined IGF‐1R in any part of the brain. The present study explored whether IGF‐1 or IGF‐1R levels are altered in human idiopathic autism. RNA and protein were extracted from post‐mortem human fusiform gyrus tissue of normal controls ( n = 20) and subjects with idiopathic autism ( n = 15). qRT‐PCR for IGF‐1 and IGF‐1R were performed, along with total IGF‐1 ELISA and IGF‐1Rβ Western blots. The levels of both IGF‐1 and IGF‐1R mRNA and protein were equivalent between the two groups, suggesting that although IGF‐1 may be useful for ASD treatment, IGF‐1 and IGF‐1R are not implicated in the pathogenesis of idiopathic autism. Autism Res 2020, 13 : 897‐907. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: IGF‐1 is being tested for the treatment of autism and related disorders. Despite promising results, it is unknown if IGF‐1 or its receptor are present in abnormal levels in patients with autism. This study showed that patients with autism have normal levels of IGF‐1 and its receptor in the brain, suggesting that although IGF‐1 is a promising treatment, disruption of IGF‐1 levels or signaling through its receptor does not seem to be a cause of autism.