Activity-Regulated Cytoskeleton-Associated Protein Dysfunction May Contribute to Memory Disorder and Earlier Detection of Autism Spectrum Disorders

Abstract

Objective: To explore a possible role for activity-regulated cytoskeleton-associated (Arc/Arg3.1) protein in the clinical identification of children with autism. Subjects and Methods: The plasma levels of Arc/Arg3.1 in 62 boys with autism and 32 healthy boys were measured using an enzyme-linked immunosorbent assay (ELISA). The Childhood Autism Rating Scale (CARS) was used to assess the severity of autism as defined in theDiagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). The Mann-Whitney U test was used for comparisons between children with autism and healthy children. The Spearman r correlation coefficient (r) was used to determine the relationship between the CARS scores among patients with autism and different variables. Results: The mean plasma level of Arc/Arg3.1 protein in autism was 1.689 ± 0.917 pg/ml, significantly higher than that of healthy controls, i.e. 0.792 ± 1.056 pg/ml (p < 0.001). No significant relationship was found between plasma levels of Arc/Arg3.1 protein and CARS scores (r = -0.06; p > 0.05) or age (r = -0.27; p > 0.05). Conclusions: The mean plasma level of Arc/Arg3.1 protein was higher in children with autism than in controls, suggesting that Arc/Arg3.1 could be a potential early blood biomarker for diagnosis of autism.

Back-translating behavioral intervention for autism spectrum disorders to mice with blunted reward restores social abilities

“…Arc codes for activity-regulated cytoskeletal-associated protein (Arc), involved in regulating synaptic plasticity, cellular signaling, glutamate neurotransmission, and spine growth 70 , 71 . Intriguingly, levels of Arc protein were found increased in the brains of two other mouse models of ASD 72 , 73 as well as in the blood of patients with autism 74 . Deficient Arc expression, however, may also be detrimental to social behavior, as shown by impaired sociability and schizophrenia-related phenotype in mice with invalidated Arc gene 75 as well as genetic association between mutations in Arc and schizophrenia in humans 76 – 78 .…”

Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons

“…Arc expression is induced by synaptic activity and its mRNA becomes localized to active dendritic spines, where it contributes to local translation during synaptic plasticity (Farris et al, 2014). Not surprisingly, in humans, mutations in Arc are associated with multiple neurological disorders affecting synapses, including autism spectrum disorders (Alhowikan, 2016), Angelman syndrome (Cao et al, 2013), and schizophrenia (Fromer et al, 2014). While some mechanisms of Arc function, such as its involvement in trafficking of glutamate receptors during plasticity (Chowdhury et al, 2006) are beginning to be elucidated, the extent of its roles remain to be deciphered.…”

Mechanisms and consequences of subcellular RNA localization across diverse cell types

“…Disruption of trans‐synaptic Arc1 mRNA transfer leads to defective synaptic plasticity. Furthermore, genetic mutations in the human Arc protein are linked to autism 181 and schizophrenia 182 . These findings are intriguing, and suggest that we have much yet to learn about modes of RNA localization, cell types that use them and consequences of its disruption.…”