ArticleBMC pharmacology & toxicology2016
Persisting neurobehavioral effects of developmental copper exposure in wildtype and metallothionein 1 and 2 knockout mice.
Article in BMC pharmacology & toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- Metallothionein-Related Findings in Autism Spectrum Disorder: A Systematic Review and Targeted Quantitative Synthesis of Human Studies.Molecular neurobiology · 2026Pooled it
- Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1 receptors, and working memory.Behavioral neuroscience · 2022Pooled it
- Metallothionein and neurodegenerative diseases.Neural regeneration research · 2026Article
- From copper homeostasis to cuproptosis: a new perspective on CNS immune regulation and neurodegenerative diseases.Frontiers in neurology · 2025Review
- Dysfunction in atox-1 and ceruloplasmin alters labile Cu levels and consequently Cu homeostasis inFrontiers in molecular biosciences · 2024Article
- Association between gestational levels of toxic metals and essential elements and cerebral palsy in children.Frontiers in neurology · 2023Article
- Iron Metabolism and Brain Development in Premature Infants.Frontiers in physiology · 2019Review
- Isolated domains of recombinant human apo-metallothionein 1A are folded at neutral pH: a denaturant and heat-induced unfolding study using ESI-MS.Bioscience reports · 2018Article
- Residue Modification and Mass Spectrometry for the Investigation of Structural and Metalation Properties of Metallothionein and Cysteine-Rich Proteins.International journal of molecular sciences · 2017Review
- Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies.Frontiers in neuroscience · 2017Review
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundMetallothioneins (MT) are small proteins, which are crucial for the distribution of heavy and transition metals. Previously, we found in mice that knockout of MT 1 and 2 genes (MTKO) impaired spatial learning and potentiated the learning impairment caused by developmental mercury exposure. The current study examined the neurocognitive and neurochemical effects of MTKO with the developmental copper (Cu) supplementation.
methodsWildtype (WT) and MTKO mice were given supplemental Cu (0, 10 or 50 mg/l) in their drinking water during gestation and until weaning. When the mice were young adults they were trained on the win-shift 8-arm radial maze test of spatial learning and memory. After cognitive testing, their brains were analyzed for norepinepherine, dopamine and serotonin levels.
resultsIn the spatial learning test, wildtype mice showed the normal sex difference with males performing more accurately than the females. This effect was eliminated by MTKO and restored by moderate Cu supplementation during development. In neurochemical studies, MTKO caused a significant overall increase in serotonin in all of the regions studied: the frontal cortex, posterior cortex, hippocampus, striatum, midbrain, and brainstem. MTKO also caused a significant increase in norepinepherine in the brainstem and hippocampus. In wildtype mice, Cu supplementation during development caused a significant decline in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex. These effects were blocked by MTKO.
conclusionsThe normal sex difference in spatial working memory accuracy, which was eliminated by MTKO, was restored by moderate copper supplementation. MTKO increased serotonin across all brain areas studied and increased norepinepherine only in the hippocampus and brainstem. MTKO blocked copper-induced decreases in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.