Alterations of Mitochondrial Biology in the Oral Mucosa of Chilean Children with Autism Spectrum Disorder (ASD)

Abstract

Autistic Spectrum Disorder (ASD) is characterized by the impairment of socio-communicative skills and the presence of restricted and stereotyped behavior patterns. Recent researches have revealed the influence of mitochondrial physiology on the development of ASD. Several research groups have identified defects in respiratory complexes, coenzyme-Q10 deficiency, increased oxidative damage, decreased of superoxide dismutase (SOD2). A study on the influence of mitochondrial physiology on the development of ASD can provide new alternatives and challenges. That is why we set ourselves the general objective to initiate studies of mitochondrial physiology in Chilean children with ASD. A sample of oral mucosa was collected in a group of 12 children diagnosed with ASD and 12 children without ASD. In children with ASD, we found a significant increase in mitochondrial DNA levels. Likewise, in these children, an increase in the protein oxidation was observed. Finally, a downward trend in the expression of the HIGD2A and SOD2 genes was observed, while DRP1, FIS1, MFN1, MFN2, and OPA1 gene expression show an upward trend. The increment of mitochondrial DNA, high oxidative stress, and high expression of the MFN2 gene could help as a scanner of the mitochondrial function in children with ASD.

Alterations of mitochondrial bioenergetics, dynamics, and morphology support the theory of oxidative damage involvement in autism spectrum disorder

“…This is in line with the fact that a shift toward fusion enables the cell to fulfill energy demand through extended mitochondrial filaments and enhanced cristae density 7 . Of note, our results on the gene expression of the mitochondrial dynamics factors are comparable with those showed in a recent study from another group that reported an upward trend in the expression of the MFN1, dynamin‐like 120 kDa protein, mitochondrial (OPA1), DRP1, and FIS1 genes coupled with significant increased expression of MFN2 gene in the oral mucosa of ASD children 35 . However, in contrast to our data, Tang et al 36 found an altered expression of mitochondrial dynamics proteins in ASD brain, with decreased levels of MFN1, MFN2, OPA1, and increased levels of DRP1 and FIS1.…”

Developmental regression and mitochondrial function in children with autism

“…ASD/No‐DR participants demonstrated less mtDNA damage compared to ASD/DR. Although mtDNA damage has not been examined in ASD in the past, other studies have noted an increased mtDNA copy number in leukocytes 6,7,43–45 and buccal mucosa 46 . An increase in overall mtDNA content is believed to be a compensatory reaction that maintains adequate wild‐type mtDNA in the face of high levels of oxidative stress which itself can damage and cause deletions in mtDNA 7 .…”

The Mitochondrial Dysfunction Hypothesis in Autism Spectrum Disorders: Current Status and Future Perspectives

“…Therefore, abnormalities in the respiratory electron transport chain during the first stage of development may be involved in the etiology of neurodevelopmental disorders. Interestingly, dysfunctions have been found in nuclear genes that encode for proteins specifically involved in mitochondrial fission and fusion, such as MFN1, MFN2, OPA1, and that are involved in mitochondrial dynamics [30]. Mitochondria are dynamic organelles, constantly changing their morphology or shape by undergoing fission (fragmentation) and fusion (elongation).…”

“…Carrasco M. et al, 2019 [30] 12 children with ASD (11 male, 1 female) 12 children without ASD Descriptive transactional and non-probabilistic design to study mtDNA in the oral mucosa of children with ASD mtDNA analysis performed with quantitative PCR (qPCR). Genotyping of the Ala16Val-SOD2 Single Nucleotide Polymorphism (SNP) polymorphism was performed by PCR using the DNA from the oral mucosa sample and a "Tetra-Primer ARMS-PCR" assay.…”

“…In this paper, the authors proposed a non-invasive procedure to assess mitochondrial DNA function in children with ASD, through the use of oral mucosa [30]. Generally, the evaluation of mitochondrial function requires an invasive biopsy, whereas the employment of this non-invasive procedure is a valid alternative, since the oral mucosa derives from the embryonic ectoderm, making them a relevant tissue for ASD studies.…”