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Autism and mitochondrial dysfunction

The previous article highlighted the complex nature of autism-spectrum disorders and the interactions of genetics and environment that play a part in their development. Autism-spectrum disorders are a complex and heterogeneous set of disorders with different causes and likely different degrees of genetic and environmental influences.

At the level of the cell, interaction between the genetics of the cell and its environment are partially mediated by mitochondria. Autism-spectrum disorders are linked to defects in neurodvelopment. Neurodevelopment is highly dependent on energy and it has been demonstrated in various recent studies that mitochondrial dysfunction is a feature of some autism-spectrum disorders.

In a study of 2 to 5 year old children participating in the Childhood Autism Risk From Genes and Environment study in California, it was confirmed that children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than non-autistic children.

One way in which mitochondrial dysfunction could contribute to autism-spectrum disorders would be via abnormal brain bioenergetics. Another study confirmed that in brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients in the Autism Tissue Program, USA, there were alterations in expression of several genes associated with mitochonrial dysfunction in brainregions of autistic subjects.

One role of mitochondria is to synthesise mitochondrial ATP and other mitokines that communicate with neighbouring cells via purinergic signaling. This conveys messages to these cells about cellular health or danger signals. In a study of a poly(IC) mouse model of autism spectrum disorders, it was found that treatment with suramin, which is a purinergic antagonist, corrected several multisystem abnormalities that are used to define autism-spectrum disorder phenotype in this mouse model.

Clearly mitochondrial dysfunction is emerging as another element of the complex genetic background of autism-spectrum disorders. Difficulty in accessing brain samples for autism-specific disorders has led some researchers to consider other accessible nonbrain resources which could be used in biomarker identification. Gene array studies in lymphoblastoid cell line-derived RNAs from have suggested potential changes in the alternative splcing of transcripts in autism compared with controls, for example in CYFIP1, a previously reported autism susceptibility gene. These kinds of studies are of vital importance in helping us get to the heart of the biological basis of autism.

Sources

ANITHA, A. et al., 2013. Downregulation of the expression of mitochondrial electron transport complex genes in autism brains. Switzerland: International Society of Neuropathology.

ANITHA, A. et al., 2012. Brain region-specific altered expression and association of mitochondria-related genes in autism. England: BioMed Central.

GIULIVI, C. et al., 2010. Mitochondrial dysfunction in autism. JAMA: The Journal Of The American Medical Association, 304(21), pp. 2389-2396

NAVIAUX, R.K. et al., 2013. Antipurinergic therapy corrects the autism-like features in the poly(IC) mouse model. Plos One, 8(3), pp. e57380-e57380

TALEBIZADEH, Z., ALDENDERFER, R. and WEN CHEN, X., 2013. A proof-of-concept study: exon-level expression profiling and alternative splicing in autism using lymphoblastoid cell lines. Psychiatric genetics