ArticlePharmacology, biochemistry, and behavior2022
Manganese-induced hyperactivity and dopaminergic dysfunction depend on age, sex and YAC128 genotype.
Article in Pharmacology, biochemistry, and behavior, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Vitamin C Transport Deficiency Alters Striatal Dopamine Gene Expression and Metabolism in YAC128 Huntington Disease Mice.Genes, brain, and behavior · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Signal Transduction Associated with Mn-induced Neurological Dysfunction.Biological trace element research · 2024Review
- Circadian Interventions in Preclinical Models of Huntington's Disease: A Narrative Review.Biomedicines · 2024Review
- Manganese in autism spectrum disorder and attention deficit hyperactivity disorder: The state of the art.Current research in toxicology · 2024Review
- Scientific opinion on the tolerable upper intake level for manganese.EFSA journal. European Food Safety Authority · 2023Article
- Widespread selenium deficiency in the brain of cases with Huntington's disease presents a new potential therapeutic target.EBioMedicine · 2023Article
- Exposing the role of metals in neurological disorders: a focus on manganese.Trends in molecular medicine · 2022Review
- Early-life manganese exposure during multiple developmental periods and adolescent verbal learning and memory.Neurotoxicology and teratologyArticle
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Manganese (Mn) is an essential micronutrient but is neurotoxic in excess. Environmental and genetic factors influence vulnerability to Mn toxicity, including sex, age, and the autosomal dominant mutation that causes Huntington disease (HD). To better understand the differential effects of Mn in wild-type (WT) versus YAC128 mice, we examined impacts of Mn exposure across different ages and sexes on disease-relevant behavioral tasks and dopamine dynamics. Young (3-week) and aged (12-month) WT and YAC128 mice received control (70 ppm) or high (2400 ppm) Mn diet for 8 weeks followed by a battery of behavioral tasks. In young female WT mice, high Mn diet induced hyperactivity across two independent behavioral tasks. Changes in the expression of tyrosine hydroxylase (TH) were consistent with the behavioral data in young females such that elevated TH in YAC128 on control diet was decreased by high Mn diet. Aged YAC128 mice showed the expected disease-relevant behavioral impairments in females and decreased TH expression, but we observed no significant effects of Mn diet in either genotype of the aged group. Fast-scan cyclic voltammetry recorded dopamine release and clearance in the nucleus accumbens of eight-month-old WT and YAC128 mice following acute Mn exposure (3×/1 week subcutaneous injections of 50 mg/kg MnCl[2]-tetrahydrate or saline). In WT mice, Mn exposure led to faster dopamine clearance that resembled saline treated YAC128 mice. Mn treatment increased dopamine release only in YAC128 mice, possibly indirectly correcting the faster dopamine clearance observed in saline treated YAC128 mice. The same exposure paradigm led to decreased dopamine and serotonin and metabolites (3-MT, HVA and 5-HIAA) in striatum and increased glutamate in YAC128 mice but not WT mice. These studies confirm an adverse effect of Mn in young, female WT animals and support a role for Mn exposure in stabilizing dopaminergic dysfunction and motivated behavior in early HD.
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