biostudies-literatureWilcox JMNICHD NIH HHSNIA NIH HHSNIEHS NIH HHSNational Cancer InstituteNCI NIH HHSNational Institutes of HealthNIH HHSVanderbilt University Medical Center94-105https://www.ebi.ac.uk/biostudies/studies/S-EPMC8761387biostudies-literatureUnknown87Manganese (Mn) is an essential micronutrient but excessive levels induce neurotoxic effects. Increasing evidence suggests a deficit of bioavailable Mn in Huntington disease (HD), an inherited neurodegenerative disease characterized by motor and cognitive disturbances. Previous studies have shown rescue of some molecular HD phenotypes by acute Mn exposure. This study simultaneously examined the potential for chronic Mn exposure to attenuate HD behavioral phenotypes, and for the HD genotype to offer protection against detrimental effects of chronic Mn exposure. In two independent studies a chronic Mn exposure paradigm was implemented in the YAC128 mouse model of HD and behavior was assessed at several timepoints. Study 1 exposed WT and YAC128 mice to twice weekly subcutaneous injections of 0NeurotoxicologyYAC128 mouse model of Huntington disease is protected against subtle chronic manganese (Mn)-induced behavioral and neuropathological changes.PMC8761387S10 OD023475-01A1R01 ES016931S10 OD023475T32 AG058524P50 HD103537P30 CA0684855P30 CA68485-19T32 ES007028R01 ES031401Wilcox JMPfalzer ACDebbiche IFHarrison FECox ECBowman ABErikson KMTienda AATotten MSfalseYAC128 mouse model of Huntington disease is protected against subtle chronic manganese (Mn)-induced behavioral and neuropathological changes.Manganese (Mn) is an essential micronutrient but excessive levels induce neurotoxic effects. Increasing evidence suggests a deficit of bioavailable Mn in Huntington disease (HD), an inherited neurodegenerative disease characterized by motor and cognitive disturbances. Previous studies have shown rescue of some molecular HD phenotypes by acute Mn exposure. This study simultaneously examined the potential for chronic Mn exposure to attenuate HD behavioral phenotypes, and for the HD genotype to offer protection against detrimental effects of chronic Mn exposure. In two independent studies a chronic Mn exposure paradigm was implemented in the YAC128 mouse model of HD and behavior was assessed at several timepoints. Study 1 exposed WT and YAC128 mice to twice weekly subcutaneous injections of 02021-01-01T00:00:00Z2021 Dec2025-04-05T09:43:57.658Z2025-04-05T09:43:57.658ZS-EPMC87613873454368110.1016/j.neuro.2021.09.002