Isotopic composition of serum zinc and copper in healthy children and children with autism spectrum disorder in North America

Miller, Kerri; Day, Patrick L.; Behl, Supriya; Stromback, Lindsay R.; Delgado, Adriana; Jannetto, Paul J.; Wieser, Michael E.; Mehta, Sunil; Pandey, Mukesh K.

doi:10.3389/fnmol.2023.1133218

Cited by 1 publication

(2 citation statements)

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“…Wilson's disease is a disorder in which mutations in the copper transporter ATP7B cause copper to accumulate in the body, resulting in motor and cognitive dysfunction, decreased motivation, and other psychiatric symptoms (31,32). However, in ASD, no conclusion has been reached about the increase or decrease of copper, and previous studies have used different samples such as whole blood, serum, hair, and saliva, as well as the races, regions, and measurement methods of the subjects, and there have been various reports of increases, no differences, or decreases (18,21,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Additionally, the altered zinc-copper metabolic rhythmicity precedes the emergence of ASD (46).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the altered zinc-copper metabolic rhythmicity precedes the emergence of ASD (46). Focusing on copper in blood samples from ASD individuals, an increased copper have been reported in serum of Chinese children with ASD (34), in plasma of autistic, Asperger's and PDD-NOS Individuals from the USA (37), in serum of autistic Individuals from Venezuela (38), or in plasma of ASD Individuals from China (21), in plasma of Autistic Children from India (39), in serum of ASD children from Russia (40), on the other hand, there are reports of no significant changes of copper in serum of children with ASD in Slovenia (41), serum of ASD children from the USA (42), whole blood of ASD children from Romania (43), in serum of ASD children from North America (44). Remarkably, consistent with our results, there was a report showing decreased copper in serum of ASD children from Chinese Han Population using about 100 samples in each group (45).…”

Section: Discussionmentioning

confidence: 99%

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Copper-deficiency is associated with impairments in social behavior and oligodendrocyte development via mTOR signaling pathway

Usui,

Doi,

Berto

et al. 2023

Preprint

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Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by impaired social communication and restricted repetitive behaviors, however the biological mechanisms remain unclear. Although trace elements play essential roles in the living body, it is unclear how alterations of trace elements in ASD are involved in pathogenesis. Here we analyzed the plasma metallome and identified the alterations of 11 elements in individuals with ASD. The copper decrease was negatively correlated with ASD symptom scores. A copper-deficient mouse model reflecting the condition showed ASD-like behaviors and impaired oligodendrocyte development. In copper-deficient mice, mechanistic target of rapamycin (mTOR) signaling was reduced, and its activation by agonist improved social impairment and oligodendrocyte developmental defects. Supporting these results, white matter volumes were negatively correlated with social symptoms in individuals with ASD. Our results demonstrate that copper-deficiency contributes to ASD by causing oligodendrocytes impairment via mTOR signaling. Our findings indicate that the effects of copper-deficiency and mTOR imbalance are relevant to the pathogenesis of ASD and are potential therapeutic targets.

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