Gene expression study of mitochondrial complex I in autism spectrum disorder

Background and Aim : Autism spectrum disorder (ASD) is known as a neurodevelopmental disorder with difficulty in social relationships, Verbal and non-verbal communication and Repetitive and ritualistic behaviors. Although genetics is known as the primary cause of autism, but it is still not clear which genes and molecular mechanisms is effective in the pathogenesis of these disease. Mitochondrial complexes role in aetiology of psychiatric disorders such as schizophrenia had been reported. The present study aimed to assess the role of mitochondrial complex I and cell bioenergetic pathways in the aetiology and characteristics of ASD.Methods : mRNA levels of all genomic and mitochondrial genes which encode mitochondrial complex I subunits (44 genes) were assessed in blood in 1594 ASD patients and 1284 non-psychiatric subjects using Real-time PCR, and also three domains of executive functions (working memory, response inhibition and vigilance) were examined by using Cambridge neuropsychological test automated battery (CANTABexpedio)in all subjects.Results : Significant expression changes of 7 genes (including NDUFS1,NDUFV1, NDUFB11, and NDUFA1) in ASD patients were detected in mitochondrial complex I. Most of these genes were novel candidate genes for ASD. Several correlations between mRNA levels and severity of symptoms, deficits in attention, working memory, response inhibition and brain activities were found.Conclusion : Deregulations of both core and supernumerary subunits of complex I are involved in the aetiology of ASD. Up- and down-regulation of mRNA levels of both core and supernumerary subunits may lead to abnormal structure,assembly or functions in complex I. This abnormal complex I may lead to electron transport chain problems in the prefrontal cortex and neurodegeneration. Correlations were found between attention and memory deficiencies and complex I abnormalities. It could lead to better understanding the role of neuronal bioenergetics system in executive function performances.

Keywords:

Autism , complex 1 , CANTAB