#METABOLOMICS WORKBENCH Codreags00_20240418_110318 DATATRACK_ID:4783 STUDY_ID:ST003176 ANALYSIS_ID:AN005214 PROJECT_ID:PR001975 VERSION 1 CREATED_ON 12-06-2024 #PROJECT PR:PROJECT_TITLE Chronic manganese exposure disrupts glutamatergic signaling and alters behavior PR:PROJECT_TITLE in APP/PSEN1 mice. PR:PROJECT_TYPE Untargeted Metabolomics analysis PR:PROJECT_SUMMARY Pathological changes in Alzheimerâs disease (AD) begin decades before PR:PROJECT_SUMMARY cognitive symptoms appear. Chronic exposure to environmental neurotoxins like PR:PROJECT_SUMMARY manganese (Mn) from sources such as air pollution and water can impact disease PR:PROJECT_SUMMARY development across decades. Mn toxicity can lead to motor and neuropsychiatric PR:PROJECT_SUMMARY symptoms resembling Parkinson's disease, attributed to its accumulation in PR:PROJECT_SUMMARY globus pallidus. In contrast, the impact of chronic lower-level exposures on PR:PROJECT_SUMMARY normal and neuropathological brain function is unknown. We tested whether 10 PR:PROJECT_SUMMARY months of a high Mn diet (2400 ppm) could alter aspects of glutamate signaling PR:PROJECT_SUMMARY in APP/PSEN1 mice to further exacerbate cognitive impairments compared to PR:PROJECT_SUMMARY control fed animals (70 ppm). This study supports the potential role for chronic PR:PROJECT_SUMMARY environmental exposures in the development of Alzheimerâs disease associated PR:PROJECT_SUMMARY neuropathology. PR:INSTITUTE Vanderbilt University PR:DEPARTMENT Chemistry PR:LABORATORY Center for Innovative Technology PR:LAST_NAME CODREANU PR:FIRST_NAME SIMONA PR:ADDRESS 1234 STEVENSON CENTER LANE PR:EMAIL SIMONA.CODREANU@VANDERBILT.EDU PR:PHONE 6158758422 PR:DOI http://dx.doi.org/10.21228/M8F723 #STUDY ST:STUDY_TITLE Chronic manganese exposure disrupts glutamatergic signaling and alters behavior ST:STUDY_TITLE in APP/PSEN1 mice. ST:STUDY_TYPE untargeted metabolomics analysis ST:STUDY_SUMMARY Pathological changes in Alzheimerâs disease (AD) begin decades before ST:STUDY_SUMMARY cognitive symptoms appear. Chronic exposure to environmental neurotoxins like ST:STUDY_SUMMARY manganese (Mn) from sources such as air pollution and water can impact disease ST:STUDY_SUMMARY development across decades. Mn toxicity can lead to motor and neuropsychiatric ST:STUDY_SUMMARY symptoms resembling Parkinson's disease, attributed to its accumulation in ST:STUDY_SUMMARY globus pallidus. In contrast, the impact of chronic lower-level exposures on ST:STUDY_SUMMARY normal and neuropathological brain function is unknown. We tested whether 10 ST:STUDY_SUMMARY months of a high Mn diet (2400 ppm) could alter aspects of glutamate signaling ST:STUDY_SUMMARY in APP/PSEN1 mice to further exacerbate cognitive impairments compared to ST:STUDY_SUMMARY control fed animals (70 ppm). This study supports the potential role for chronic ST:STUDY_SUMMARY environmental exposures in the development of Alzheimerâs disease associated ST:STUDY_SUMMARY neuropathology. ST:INSTITUTE Vanderbilt University ST:DEPARTMENT Chemistry ST:LABORATORY Center for Innovative Technology ST:LAST_NAME CODREANU ST:FIRST_NAME SIMONA ST:ADDRESS 1234 STEVENSON CENTER LANE ST:EMAIL SIMONA.CODREANU@VANDERBILT.EDU ST:PHONE 6158758422 ST:SUBMIT_DATE 2024-04-18 #SUBJECT SU:SUBJECT_TYPE Mammal SU:SUBJECT_SPECIES Mus musculus SU:TAXONOMY_ID 10090 SU:GENOTYPE_STRAIN APP/PSEN1 and WT SU:AGE_OR_AGE_RANGE 12 months old SU:GENDER Male and female SU:ANIMAL_ANIMAL_SUPPLIER Jackson Laboratories SU:SPECIES_GROUP Mammals #SUBJECT_SAMPLE_FACTORS: SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Additional sample data SUBJECT_SAMPLE_FACTORS 2716 C1 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_High_C1 SUBJECT_SAMPLE_FACTORS 2716 C1n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_High_C1 SUBJECT_SAMPLE_FACTORS 2713 C2 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_High_C2 SUBJECT_SAMPLE_FACTORS 2713 C2n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_High_C2 SUBJECT_SAMPLE_FACTORS 2717 C3 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_High_C3 SUBJECT_SAMPLE_FACTORS 2717 C3n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_High_C3 SUBJECT_SAMPLE_FACTORS 2947 C4 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_High_C4 SUBJECT_SAMPLE_FACTORS 2947 C4n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_High_C4 SUBJECT_SAMPLE_FACTORS 2918 C10 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C10 SUBJECT_SAMPLE_FACTORS 2918 C10n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C10 SUBJECT_SAMPLE_FACTORS 2973 C11 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C11 SUBJECT_SAMPLE_FACTORS 2973 C11n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C11 SUBJECT_SAMPLE_FACTORS 2976 C12 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C12 SUBJECT_SAMPLE_FACTORS 2976 C12n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C12 SUBJECT_SAMPLE_FACTORS 2594 C5 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C5 SUBJECT_SAMPLE_FACTORS 2594 C5n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C5 SUBJECT_SAMPLE_FACTORS 2595 C6 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C6 SUBJECT_SAMPLE_FACTORS 2595 C6n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C6 SUBJECT_SAMPLE_FACTORS 2720 C7 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C7 SUBJECT_SAMPLE_FACTORS 2720 C7n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C7 SUBJECT_SAMPLE_FACTORS 2915 C8 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C8 SUBJECT_SAMPLE_FACTORS 2915 C8n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C8 SUBJECT_SAMPLE_FACTORS 2917 C9 Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_PS1_Low_C9 SUBJECT_SAMPLE_FACTORS 2917 C9n Sample source:Brain-Cortex | Sex:Female | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_PS1_Low_C9 SUBJECT_SAMPLE_FACTORS 2589 C13 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_High_C13 SUBJECT_SAMPLE_FACTORS 2589 C13n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_High_C13 SUBJECT_SAMPLE_FACTORS 2590 C14 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_High_C14 SUBJECT_SAMPLE_FACTORS 2590 C14n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_High_C14 SUBJECT_SAMPLE_FACTORS 2591 C15 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_High_C15 SUBJECT_SAMPLE_FACTORS 2591 C15n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_High_C15 SUBJECT_SAMPLE_FACTORS 2712 C16 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_High_C16 SUBJECT_SAMPLE_FACTORS 2712 C16n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_High_C16 SUBJECT_SAMPLE_FACTORS 2715 C17 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_High_C17 SUBJECT_SAMPLE_FACTORS 2715 C17n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_High_C17 SUBJECT_SAMPLE_FACTORS 2958 C18 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_High_C18 SUBJECT_SAMPLE_FACTORS 2958 C18n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_High_C18 SUBJECT_SAMPLE_FACTORS 2949 C19 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_High_C19 SUBJECT_SAMPLE_FACTORS 2949 C19n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_High_C19 SUBJECT_SAMPLE_FACTORS 2593 C20 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C20 SUBJECT_SAMPLE_FACTORS 2593 C20n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C20 SUBJECT_SAMPLE_FACTORS 2596 C21 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C21 SUBJECT_SAMPLE_FACTORS 2596 C21n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C21 SUBJECT_SAMPLE_FACTORS 2721 C22 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C22 SUBJECT_SAMPLE_FACTORS 2721 C22n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C22 SUBJECT_SAMPLE_FACTORS 2916 C23 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C23 SUBJECT_SAMPLE_FACTORS 2916 C23n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C23 SUBJECT_SAMPLE_FACTORS 2961 C24 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C24 SUBJECT_SAMPLE_FACTORS 2961 C24n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C24 SUBJECT_SAMPLE_FACTORS 2962 C25 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C25 SUBJECT_SAMPLE_FACTORS 2962 C25n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C25 SUBJECT_SAMPLE_FACTORS 2974 C26 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C26 SUBJECT_SAMPLE_FACTORS 2974 C26n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C26 SUBJECT_SAMPLE_FACTORS 2975 C27 Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_F_WT_Low_C27 SUBJECT_SAMPLE_FACTORS 2975 C27n Sample source:Brain-Cortex | Sex:Female | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_F_WT_Low_C27 SUBJECT_SAMPLE_FACTORS 2584 C28 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_High_C28 SUBJECT_SAMPLE_FACTORS 2584 C28n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_High_C28 SUBJECT_SAMPLE_FACTORS 2585 C29 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_High_C29 SUBJECT_SAMPLE_FACTORS 2585 C29n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_High_C29 SUBJECT_SAMPLE_FACTORS 2965 C30 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_High_C30 SUBJECT_SAMPLE_FACTORS 2965 C30n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_High_C30 SUBJECT_SAMPLE_FACTORS 2969 C31 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_High_C31 SUBJECT_SAMPLE_FACTORS 2969 C31n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_High_C31 SUBJECT_SAMPLE_FACTORS 2968 C32 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_High_C32 SUBJECT_SAMPLE_FACTORS 2968 C32n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_High_C32 SUBJECT_SAMPLE_FACTORS 2703 C33 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_Low_C33 SUBJECT_SAMPLE_FACTORS 2703 C33n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_Low_C33 SUBJECT_SAMPLE_FACTORS 2718 C34 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_Low_C34 SUBJECT_SAMPLE_FACTORS 2718 C34n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_Low_C34 SUBJECT_SAMPLE_FACTORS 2729 C35 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_Low_C35 SUBJECT_SAMPLE_FACTORS 2729 C35n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_Low_C35 SUBJECT_SAMPLE_FACTORS 2951 C36 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_Low_C36 SUBJECT_SAMPLE_FACTORS 2951 C36n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_Low_C36 SUBJECT_SAMPLE_FACTORS 2952 C37 Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_PS1_Low_C37 SUBJECT_SAMPLE_FACTORS 2952 C37n Sample source:Brain-Cortex | Sex:Male | Genotype:PS1 | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_PS1_Low_C37 SUBJECT_SAMPLE_FACTORS 2586 C38 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C38 SUBJECT_SAMPLE_FACTORS 2586 C38n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C38 SUBJECT_SAMPLE_FACTORS 2587 C39 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C39 SUBJECT_SAMPLE_FACTORS 2587 C39n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C39 SUBJECT_SAMPLE_FACTORS 2600 C40 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C40 SUBJECT_SAMPLE_FACTORS 2600 C40n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C40 SUBJECT_SAMPLE_FACTORS 2953 C41 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C41 SUBJECT_SAMPLE_FACTORS 2953 C41n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C41 SUBJECT_SAMPLE_FACTORS 2954 C42 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C42 SUBJECT_SAMPLE_FACTORS 2954 C42n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C42 SUBJECT_SAMPLE_FACTORS 2955 C43 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C43 SUBJECT_SAMPLE_FACTORS 2955 C43n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C43 SUBJECT_SAMPLE_FACTORS 2957 C44 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C44 SUBJECT_SAMPLE_FACTORS 2957 C44n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C44 SUBJECT_SAMPLE_FACTORS 2966 C45 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C45 SUBJECT_SAMPLE_FACTORS 2966 C45n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C45 SUBJECT_SAMPLE_FACTORS 2597 C53 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_High_C53 SUBJECT_SAMPLE_FACTORS 2597 C53n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:High RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_High_C53 SUBJECT_SAMPLE_FACTORS 2704 C46 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_Low_C46 SUBJECT_SAMPLE_FACTORS 2704 C46n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_Low_C46 SUBJECT_SAMPLE_FACTORS 2727 C47 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_Low_C47 SUBJECT_SAMPLE_FACTORS 2728 C48 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_Low_C48 SUBJECT_SAMPLE_FACTORS 2728 C48n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_Low_C48 SUBJECT_SAMPLE_FACTORS 2950 C49 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_Low_C49 SUBJECT_SAMPLE_FACTORS 2950 C49n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_Low_C49 SUBJECT_SAMPLE_FACTORS 2956 C50 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_Low_C50 SUBJECT_SAMPLE_FACTORS 2956 C50n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_Low_C50 SUBJECT_SAMPLE_FACTORS 2970 C51 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_Low_C51 SUBJECT_SAMPLE_FACTORS 2970 C51n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_Low_C51 SUBJECT_SAMPLE_FACTORS 2971 C52 Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230117_aHILICp_M_WT_Low_C52 SUBJECT_SAMPLE_FACTORS 2971 C52n Sample source:Brain-Cortex | Sex:Male | Genotype:WT | Mn Treatment:Low RAW_FILE_NAME(MS_Samples)=SC_20230123_HILICn_M_WT_Low_C52 #COLLECTION CO:COLLECTION_SUMMARY Following euthanasia by terminal anesthesia with isoflurane followed by CO:COLLECTION_SUMMARY decapitation, the brains were quickly removed and divided into two hemispheres. CO:COLLECTION_SUMMARY One hemisphere was dissected into distinct brain areas including cortex and snap CO:COLLECTION_SUMMARY frozen before long term storage at -80 ºC. The second hemisphere was immersion CO:COLLECTION_SUMMARY fixed in 4% paraformaldehyde for at least 24 hours before being placed in 30% CO:COLLECTION_SUMMARY sucrose for 24-72 hours and then moved to 1xPBS. CO:COLLECTION_PROTOCOL_FILENAME Tissue_acquisition_Cortex.pdf CO:SAMPLE_TYPE Brain cortex CO:STORAGE_CONDITIONS -80â #TREATMENT TR:TREATMENT_SUMMARY Mice were maintained on standard lab chow (Purina 5001) which contains 70 ppm Mn TR:TREATMENT_SUMMARY until 3 months of ages. Mice were then randomly allocated by cage to control (70 TR:TREATMENT_SUMMARY ppm; D17020702) or high (2400 ppm) Mn diets. Diets were formulated by Research TR:TREATMENT_SUMMARY Diets Inc. and comprised their normal control diet (D19080201) and differed only TR:TREATMENT_SUMMARY in the amount of Mn. Food levels were checked at least weekly and mice were TR:TREATMENT_SUMMARY weighed monthly to ensure normal growth. TR:TREATMENT_PROTOCOL_FILENAME Mice_and_dietary_treatment.pdf #SAMPLEPREP SP:SAMPLEPREP_SUMMARY Cortex tissue samples were analyzed via liquid chromatography-high resolution SP:SAMPLEPREP_SUMMARY tandem mass spectrometry (LC-HRMS and LC-HRMS/MS) using previously described SP:SAMPLEPREP_SUMMARY methods. Briefly, harvested cortex tissue samples were thawed on ice and lysed SP:SAMPLEPREP_SUMMARY in 500 µL ice-cold lysis buffer (1:1:2, acetonitrile: methanol: ammonium SP:SAMPLEPREP_SUMMARY bicarbonate 0.1M, pH 8.0) followed by probe tip sonication and normalized via SP:SAMPLEPREP_SUMMARY protein amount (100 µg) based on a bicinchoninic acid protein assay (Thermo SP:SAMPLEPREP_SUMMARY Fisher Scientific, Waltham, MA). Deproteinization of individual samples was SP:SAMPLEPREP_SUMMARY performed by addition of 800 µL of ice-cold methanol following the addition of SP:SAMPLEPREP_SUMMARY isotopically labeled standards (phenylalanine-D8, biotin-D2 and lauryl SP:SAMPLEPREP_SUMMARY carnitine-D3) to determine sample process variability. Precipitated proteins SP:SAMPLEPREP_SUMMARY were centrifuged at 10,000 rpm for 10 min after overnight incubation at -80°C. SP:SAMPLEPREP_SUMMARY Metabolite extracts were dried in vacuo and further purified via liquid-liquid SP:SAMPLEPREP_SUMMARY extraction (LLE) method with tert-Butyl methyl ether (MTBE). The hydrophilic SP:SAMPLEPREP_SUMMARY fraction of each sample extract was transferred into a new Eppendorf tube, dried SP:SAMPLEPREP_SUMMARY in vacuo, and stored at -80°C until further use. SP:SAMPLEPREP_PROTOCOL_FILENAME MS_Methods_Cortex.pdf SP:PROCESSING_STORAGE_CONDITIONS -80â SP:EXTRACT_STORAGE -80â #CHROMATOGRAPHY CH:CHROMATOGRAPHY_SUMMARY Hydrophilic separation CH:METHODS_FILENAME MS_Methods_Cortex.pdf CH:INSTRUMENT_NAME Thermo Vanquish CH:COLUMN_NAME Waters ACQUITY UPLC BEH Amide (100 x 2.1mm,1.7um) CH:COLUMN_TEMPERATURE 30 CH:FLOW_GRADIENT 30 min; 95%A, 5%B CH:FLOW_RATE 0.20 mL/min CH:SOLVENT_A 90% water, 10% acetonitrile; 5mM Ammonium Formate, 0.1%FA CH:SOLVENT_B 10% water, 90% acetonitrile; 5mM Ammonium Formate, 0.1%FA CH:CHROMATOGRAPHY_TYPE HILIC #ANALYSIS AN:ANALYSIS_TYPE MS AN:ANALYSIS_PROTOCOL_FILE MS_Methods_Cortex.pdf #MS MS:INSTRUMENT_NAME Thermo Q Exactive HF hybrid Orbitrap MS:INSTRUMENT_TYPE Orbitrap MS:MS_TYPE ESI MS:MS_COMMENTS MS were acquired in both, positive and negative modes Progenesis QI v.3.0 MS:MS_COMMENTS (Non-linear Dynamics, Newcastle, UK) was used to review, process and normalize MS:MS_COMMENTS the mass spectrometry data. The pooled QC sample was used to align all MS and MS:MS_COMMENTS MS/MS sample runs. MS:ION_MODE NEGATIVE MS:MS_RESULTS_FILE ST003176_AN005214_Results.txt UNITS:peak intensity Has m/z:Yes Has RT:Yes RT units:Minutes #END