Autism Spectrum Disorders and Metal Dyshomeostasis, Volume II

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Background

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder. According to the center for disease control (CDC) in the USA, 1 out of 54 children is identified with ASD. From a global perspective, 0.76% of children are detected with ASD.

ASD etiology is complex and appears to be a mixture of environmental co-factors and genetic factors underlying ASD. Genetic mutations account for 69% of the risk, suggesting that environmental factors account for 31%. Among the environmental factors, at present, 52 potential biomarkers and 67 environmental factors are recognized as the risk factors. Identified biomarkers are non-genetic in origin, but various risk factors such as a family history of psoriasis, and rheumatoid arthritis are genetic in nature.

Among the environmental risk factors linked to ASD are the uses of antidepressant and serotonin reuptake inhibitors during pregnancy, paternal and maternal factors (age and age differences), and serum zinc levels. However, one of the most convincing factors is late pregnancy, in women over 35 years of age. In this context, it is noteworthy that metal ion contents may vary with age.

In particular, iron, zinc, and copper are considered as essential metal nutrients for normal neurodevelopmental processes. Iron is required by the ribonucleotide reductase enzyme that regulates the central nervous system and plays also a role in myelin synthesis. Zinc is needed for cell division because of a key role in DNA synthesis. It is also required for neuromodulation at central synapses. Zinc inhibits excitatory NMDA receptors, which play key roles in learning and memory - as well as inhibitory GABAA receptors - and acts as both a positive and negative allosteric modulator at AMPA receptors and at inhibitory Gly receptors, particularly important in cortical development.

Along with folic acid and vitamin A, copper is needed for the neural plate and neural tube formation, in early stages of development. Other essential trace metals, such as Mn, Mo, and trace elements such as Se ions also play a critical role in neurodevelopment.

Deficiency or dyshomeostasis of any of these metal ions will alter the finely-tuned neurodevelopmental process and may not be corrected even after the repletion of these metal ions.

Despite extensive research, the causative mechanisms of ASD are yet not fully explained. This is likely because of genetic heterogeneity and other factors contributing to disease development, including metal dyshomeostasis. Experimental research focusing on the impact of Zn, Cu, Se, and Fe deficiencies in ASD, will provide insights into ASD pathophysiology and deepen our knowledge of the influence of environmental co-factors on the disease.

This Research Topic aims to further dissect the impact of metal dyshomeostasis in ASD. This includes the role of metal ions in neuronal development, the effects of parental metal ion(s) deficiencies on neurodevelopment, and the role of metal ions in neuronal communication. Contributions will address, identify, and evaluate, biomarkers involving metal ions and their dyshomeostasis during neurodevelopment.

Articles dealing with heavy metal toxicity and ASD are excluded from the scope of this special issue. We welcome authors to address the following topics:

• Evidence reporting metal ion deficiencies in ASD
• The role of metal ions in neuronal development
• The role of metal ions in gene expression
• ASD-like symptoms and metal ions
• Evidence of isotopic abundance of biometals in ASD
• Role and effect of iron in ASD management
• The impact of metal ions on neuronal communication
• Potential metal ion therapy in ASD - effects of metal ion supplement on ASD treatment
• The role of AMPA, NMDA, Glycine (GlyR alpha2, cortical migration) and GABAA receptors in ASD pathophysiology
• Novel findings on the identification and role of new receptors and pathways involved in ASD pathology and metal ions regulation
• Selenoproteins in neurodevelopmental disorders: Evidence and mechanism
Novel findings on ASD therapy with clinical results are also welcome.

Taken together, experimental evidence will help us to further elucidate this developmental condition linked factors and help to tackle the disease.

Keywords: Autism Spectrum Disorder (ASD), Metal dyshomeostasis, ASD pathology, Neuronal development, Biometals: Zn- Fe- Cu- Se, #CollectionSeries

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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