Summary of Study ST001888

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001047. The data can be accessed directly via it's Project DOI: 10.21228/M8C68D This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST001888
Study Title	A Metabolome Atlas of the Aging Mouse Brain (Study part II)
Study Summary	The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remains poorly understood. To start bridging this gap, we generated a metabolome atlas of the aging wildtype male and female mouse brain from 10 anatomical regions spanning from adolescence to old age. We combined data from three chromatography-based mass spectrometry assays and structurally annotated 1,547 metabolites to reveal the underlying architecture of aging-induced changes in the brain metabolome. Overall differences between sexes were minimal. We found 99% of all metabolites to significantly differ between brain regions in at least one age group. We also discovered that 97% of the metabolome showed significant changes with respect to age groups. For example, we identified a shift in sphingolipid patterns during aging that is related to myelin remodeling in the transition from adolescent to aging brains. This shift was accompanied by large changes in overall signature in a range of other metabolic pathways. We found clear metabolic similarities in brain regions that were functionally related such as brain stem, cerebrum and cerebellum. In cerebrum, metabolic correlation patterns got markedly weaker in the transition from adolescent to adulthood, whereas the overall correlation patterns between all regions reflected a decreased brain segregation at old age. We were also able to map metabolic changes to gene and protein brain atlases to link molecular changes to metabolic brain phenotypes. Metabolic profiles can be investigated via https://mouse.atlas.metabolomics.us/. This new resource enables brain researchers to link new metabolomic studies to a foundation data set.
Institute	University of California, Davis
Department	Genome Center
Laboratory	West Coast Metabolomics Center
Last Name	Ding
First Name	Jun
Address	451 East Health Science Drive, Davis, CA, 95616, USA
Email	junding@ucdavis.edu
Phone	773-326-5420
Submit Date	2021-07-25
Raw Data Available	Yes
Raw Data File Type(s)	cdf, raw(Thermo)
Analysis Type Detail	GC-MS/LC-MS
Release Date	2021-08-30
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR001047
Project DOI:	doi: 10.21228/M8C68D
Project Title:	A Metabolome Atlas of the Aging Mouse Brain
Project Summary:	The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remains poorly understood. To start bridging this gap, we generated a metabolome atlas of the aging mouse brain from 10 anatomical regions spanning from adolescence to late adulthood. We combined data from three chromatography-based mass spectrometry assays and structurally annotated 1,709 metabolites to reveal the underlying architecture of aging-induced changes in the brain metabolome. Overall differences between sexes were minimal. We found 94% of all metabolites to significantly differ between brain sections in at least one age group. We also discovered that 90% of the metabolome showed significant changes with respect to age groups. For example, we identified a shift in sphingolipid patterns during aging that is related to myelin remodeling in the transition from adolescent to adult brains. This shift was accompanied by large changes in overall signature in a range of other metabolic pathways. We found clear metabolic similarities in brain sections that were functionally related such as brain stem, cerebrum and cerebellum. In cerebrum, metabolic correlation patterns got markedly weaker in the transition from adolescent to ear adults, whereas correlation patterns between cerebrum and brainstem regions decreased from early to late adulthood. We were also able to map metabolic changes to gene and protein brain atlases to link molecular changes to metabolic brain phenotypes. Metabolic profiles can be investigated via https://atlas.metabolomics.us/. This new resource enables brain researchers to link new metabolomic studies to a foundation data set.
Institute:	University of California, Davis
Department:	Genome Center
Laboratory:	West Coast Metabolomics Center
Last Name:	Ding
First Name:	Jun
Address:	451 East Health Science Drive, Davis, CA, 95616, USA
Email:	junding@ucdavis.edu
Phone:	773-326-5420
Funding Source:	NIH U2C ES030158

Subject:

Subject ID:	SU001966
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Genotype Strain:	C57BL/6NCrl
Age Or Age Range:	92 weeks old
Gender:	Male and female
Species Group:	Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Brain region	Gender
SA175310	900483-015-165	Basal ganglia	Female
SA175311	900483-010-110	Basal ganglia	Female
SA175312	900483-011-121	Basal ganglia	Female
SA175313	900483-016-176	Basal ganglia	Female
SA175314	900483-014-154	Basal ganglia	Female
SA175315	900483-009-099	Basal ganglia	Female
SA175316	900483-013-143	Basal ganglia	Female
SA175317	900483-012-132	Basal ganglia	Female
SA175318	900483-014-066	Basal ganglia	Male
SA175319	900483-011-033	Basal ganglia	Male
SA175320	900483-015-077	Basal ganglia	Male
SA175321	900483-012-044	Basal ganglia	Male
SA175322	900483-016-088	Basal ganglia	Male
SA175323	900483-013-055	Basal ganglia	Male
SA175324	900483-010-022	Basal ganglia	Male
SA175325	900483-009-011	Basal ganglia	Male
SA175326	900483-010-103	Cerebellum	Female
SA175327	900483-011-114	Cerebellum	Female
SA175328	900483-013-136	Cerebellum	Female
SA175329	900483-012-125	Cerebellum	Female
SA175330	900483-014-147	Cerebellum	Female
SA175331	900483-016-169	Cerebellum	Female
SA175332	900483-015-158	Cerebellum	Female
SA175333	900483-009-092	Cerebellum	Female
SA175334	900483-013-048	Cerebellum	Male
SA175335	900483-011-026	Cerebellum	Male
SA175336	900483-009-004	Cerebellum	Male
SA175337	900483-010-015	Cerebellum	Male
SA175338	900483-015-070	Cerebellum	Male
SA175339	900483-016-081	Cerebellum	Male
SA175340	900483-012-037	Cerebellum	Male
SA175341	900483-014-059	Cerebellum	Male
SA175342	900483-009-090	Cerebral cortex	Female
SA175343	900483-012-123	Cerebral cortex	Female
SA175344	900483-011-112	Cerebral cortex	Female
SA175345	900483-014-145	Cerebral cortex	Female
SA175346	900483-016-167	Cerebral cortex	Female
SA175347	900483-015-156	Cerebral cortex	Female
SA175348	900483-013-134	Cerebral cortex	Female
SA175349	900483-010-101	Cerebral cortex	Female
SA175350	900483-016-079	Cerebral cortex	Male
SA175351	900483-010-013	Cerebral cortex	Male
SA175352	900483-013-046	Cerebral cortex	Male
SA175353	900483-012-035	Cerebral cortex	Male
SA175354	900483-014-057	Cerebral cortex	Male
SA175355	900483-009-002	Cerebral cortex	Male
SA175356	900483-011-024	Cerebral cortex	Male
SA175357	900483-015-068	Cerebral cortex	Male
SA175358	900483-013-135	Hippocampus	Female
SA175359	900483-010-102	Hippocampus	Female
SA175360	900483-012-124	Hippocampus	Female
SA175361	900483-009-091	Hippocampus	Female
SA175362	900483-014-146	Hippocampus	Female
SA175363	900483-015-157	Hippocampus	Female
SA175364	900483-011-113	Hippocampus	Female
SA175365	900483-016-168	Hippocampus	Female
SA175366	900483-009-003	Hippocampus	Male
SA175367	900483-013-047	Hippocampus	Male
SA175368	900483-011-025	Hippocampus	Male
SA175369	900483-014-058	Hippocampus	Male
SA175370	900483-012-036	Hippocampus	Male
SA175371	900483-016-080	Hippocampus	Male
SA175372	900483-015-069	Hippocampus	Male
SA175373	900483-010-014	Hippocampus	Male
SA175374	900483-012-128	Hypothalamus	Female
SA175375	900483-015-161	Hypothalamus	Female
SA175376	900483-013-139	Hypothalamus	Female
SA175377	900483-011-117	Hypothalamus	Female
SA175378	900483-010-106	Hypothalamus	Female
SA175379	900483-016-172	Hypothalamus	Female
SA175380	900483-009-095	Hypothalamus	Female
SA175381	900483-014-150	Hypothalamus	Female
SA175382	900483-013-051	Hypothalamus	Male
SA175383	900483-014-062	Hypothalamus	Male
SA175384	900483-009-007	Hypothalamus	Male
SA175385	900483-012-040	Hypothalamus	Male
SA175386	900483-011-029	Hypothalamus	Male
SA175387	900483-015-073	Hypothalamus	Male
SA175388	900483-010-018	Hypothalamus	Male
SA175389	900483-016-084	Hypothalamus	Male
SA175390	900483-013-141	Medulla	Female
SA175391	900483-010-108	Medulla	Female
SA175392	900483-016-174	Medulla	Female
SA175393	900483-011-119	Medulla	Female
SA175394	900483-009-097	Medulla	Female
SA175395	900483-012-130	Medulla	Female
SA175396	900483-014-152	Medulla	Female
SA175397	900483-015-163	Medulla	Female
SA175398	900483-015-075	Medulla	Male
SA175399	900483-014-064	Medulla	Male
SA175400	900483-012-042	Medulla	Male
SA175401	900483-016-086	Medulla	Male
SA175402	900483-011-031	Medulla	Male
SA175403	900483-010-020	Medulla	Male
SA175404	900483-009-009	Medulla	Male
SA175405	900483-013-053	Medulla	Male
SA175406	900483-016-170	Midbrain	Female
SA175407	900483-011-115	Midbrain	Female
SA175408	900483-010-104	Midbrain	Female
SA175409	900483-009-093	Midbrain	Female

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Collection:

Collection ID:	CO001959
Collection Summary:	Brain tissue samples were collected from 92 weeks old male and female wild type mice on a C57BL/6N background and performed under approved institutional IACUC protocols. Briefly, mice were anesthetized with 4% Isoflurane in 100% oxygen at a flow rate of 3 L/h to a surgical plane. Blood was then collected by retro-orbital bleed into an EDTA tube and centrifuged at 3000 rpm for 15 min to separate and remove plasma. While under anesthsia mice were perfused for approximately 10 minutes with phosphate buffered saline (PBS) pH 7.4 at room temperature. Following perfusion, the brain was removed and placed in a petri dish containing PBS at 4oC for dissection of individual brain regions. A dissection microscope, fine tip (#5) forceps, and razor blade was used to isolate and separate brain regions (olfactory bulb, hippocampus, hypothalamus, thalamus, midbrain, cerebellum, pons, medulla, cerebral cortex, and basal ganglia collected as caudate putamen and basal forebrain) in induvial mice while being careful to avoid contamination from neighboring regions. Briefly, after separating the olfactory bulbs, the left and right cerebral cortices were then removed while taking care not to disrupt the regions underneath. This enabled access to and removal of the left and right hippocampus. After cutting along the thalamus, the left and right caudate putamen was separated and removed from the basal forebrain. Subsequently, the cerebellum and midbrain were isolated and removed, followed by separation and removal of the thalamus and the hypothalamus from the pons and medulla. The pons was then separated from the medulla. Any spinal cord remaining on the medulla was removed. Each region was immediately placed in a cryo vial and flash frozen in liquid nitrogen for analysis.
Sample Type:	Brain

Treatment:

Treatment ID:	TR001978
Treatment Summary:	Five milligrams of tissue from each brain region were homogenized in 225 µL of -20˚C cold, internal standard-containing methanol using a GenoGrinder 2010 (SPEX SamplePrep) for 2 min at 1,350 rpm. The homogenate was vortexed for 10 s. 750 µL of -20˚C cold, internal standard-containing methyl tertiary-butyl ether (MTBE) was added, and the mixture was vortexed for 10 s and shaken at 4˚C for 5 min with an Orbital Mixing Chilling/Heating Plate (Torrey Pines Scientific Instruments). MTBE contained cholesteryl ester 22:1 as internal standard. Next, 188 µL room temperature water was added and vortexed for 20s to induce phase separation. After centrifugation for 2min at 14,000 g, two 350 µL aliquots of the upper non-polar phase and two 125 µL aliquots of the bottom polar phase were collected and dried down. Remaining fractions were combined to form QC pools and were injected after every set of 10 biological samples. The non-polar phase employed for lipidomics was resuspended in a mixture of methanol/toluene (60 µL, 9:1, v/v) containing an internal standard [12-[(cyclohexylamino) carbonyl]amino]-dodecanoic acid (CUDA)] before injection. Resuspension of dried polar phases for HILIC analysis was performed in a mixture of internal standard-containing acetonitrile/water (90 µL, 4:1, v/v). The second dried polar phase was reserved for GC analysis and a following derivatization process was carried out before injection. First, carbonyl groups were protected by methoximation with methoxyamine hydrochloride in pyridine (40 mg/mL, 10 µL) was added to the dried samples. Then, the mixture was incubated at 30˚C for 90 min followed by trimethylsilylation with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA, 90 μL) containing C8–C30 fatty acid methyl esters (FAMEs) as internal standards by shaking at 37˚C for 30min.

Treatment ID:

TR001978

Treatment Summary:

Five milligrams of tissue from each brain region were homogenized in 225 µL of -20˚C cold, internal standard-containing methanol using a GenoGrinder 2010 (SPEX SamplePrep) for 2 min at 1,350 rpm. The homogenate was vortexed for 10 s. 750 µL of -20˚C cold, internal standard-containing methyl tertiary-butyl ether (MTBE) was added, and the mixture was vortexed for 10 s and shaken at 4˚C for 5 min with an Orbital Mixing Chilling/Heating Plate (Torrey Pines Scientific Instruments). MTBE contained cholesteryl ester 22:1 as internal standard. Next, 188 µL room temperature water was added and vortexed for 20s to induce phase separation. After centrifugation for 2min at 14,000 g, two 350 µL aliquots of the upper non-polar phase and two 125 µL aliquots of the bottom polar phase were collected and dried down. Remaining fractions were combined to form QC pools and were injected after every set of 10 biological samples. The non-polar phase employed for lipidomics was resuspended in a mixture of methanol/toluene (60 µL, 9:1, v/v) containing an internal standard [12-[(cyclohexylamino) carbonyl]amino]-dodecanoic acid (CUDA)] before injection. Resuspension of dried polar phases for HILIC analysis was performed in a mixture of internal standard-containing acetonitrile/water (90 µL, 4:1, v/v). The second dried polar phase was reserved for GC analysis and a following derivatization process was carried out before injection. First, carbonyl groups were protected by methoximation with methoxyamine hydrochloride in pyridine (40 mg/mL, 10 µL) was added to the dried samples. Then, the mixture was incubated at 30˚C for 90 min followed by trimethylsilylation with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA, 90 μL) containing C8–C30 fatty acid methyl esters (FAMEs) as internal standards by shaking at 37˚C for 30min.

Sample Preparation:

Sampleprep ID:	SP001972
Sampleprep Summary:	Five milligrams of tissue from each brain region were homogenized in 225 µL of -20˚C cold, internal standard-containing methanol using a GenoGrinder 2010 (SPEX SamplePrep) for 2min at 1,350 rpm. The homogenate was vortexed for 10s. 750 µL of -20˚C cold, internal standard-containing methyl tertiary-butyl ether (MTBE) was added, and the mixture was vortexed for 10 s and shaken at 4˚C for 5min with an Orbital Mixing Chilling/Heating Plate (Torrey Pines Scientific Instruments). MTBE contained cholesteryl ester 22:1 as internal standard. Next, 188 µL room temperature water was added and vortexed for 20s to induce phase separation. After centrifugation for 2min at 14,000 g, two 350 µL aliquots of the upper non-polar phase and two 125 µL aliquots of the bottom polar phase were collected and dried down. Remaining fractions were combined to form QC pools and were injected after every set of 10 biological samples. The non-polar phase employed for lipidomics was resuspended in a mixture of methanol/toluene (60 µL, 9:1, v/v) containing an internal standard [12-[(cyclohexylamino) carbonyl]amino]-dodecanoic acid (CUDA)] before injection. Resuspension of dried polar phases for HILIC analysis was performed in a mixture of internal standard-containing acetonitrile/water (90 µL, 4:1, v/v). The second dried polar phase was reserved for GC analysis and a following derivatization process was carried out before injection. First, carbonyl groups were protected by methoximation with methoxyamine hydrochloride in pyridine (40 mg/mL, 10 µL) was added to the dried samples. Then, the mixture was incubated at 30˚C for 90 min followed by trimethylsilylation with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA, 90 μL) containing C8–C30 fatty acid methyl esters (FAMEs) as internal standards by shaking at 37˚C for 30min.

Sampleprep ID:

SP001972

Sampleprep Summary:

Five milligrams of tissue from each brain region were homogenized in 225 µL of -20˚C cold, internal standard-containing methanol using a GenoGrinder 2010 (SPEX SamplePrep) for 2min at 1,350 rpm. The homogenate was vortexed for 10s. 750 µL of -20˚C cold, internal standard-containing methyl tertiary-butyl ether (MTBE) was added, and the mixture was vortexed for 10 s and shaken at 4˚C for 5min with an Orbital Mixing Chilling/Heating Plate (Torrey Pines Scientific Instruments). MTBE contained cholesteryl ester 22:1 as internal standard. Next, 188 µL room temperature water was added and vortexed for 20s to induce phase separation. After centrifugation for 2min at 14,000 g, two 350 µL aliquots of the upper non-polar phase and two 125 µL aliquots of the bottom polar phase were collected and dried down. Remaining fractions were combined to form QC pools and were injected after every set of 10 biological samples. The non-polar phase employed for lipidomics was resuspended in a mixture of methanol/toluene (60 µL, 9:1, v/v) containing an internal standard [12-[(cyclohexylamino) carbonyl]amino]-dodecanoic acid (CUDA)] before injection. Resuspension of dried polar phases for HILIC analysis was performed in a mixture of internal standard-containing acetonitrile/water (90 µL, 4:1, v/v). The second dried polar phase was reserved for GC analysis and a following derivatization process was carried out before injection. First, carbonyl groups were protected by methoximation with methoxyamine hydrochloride in pyridine (40 mg/mL, 10 µL) was added to the dried samples. Then, the mixture was incubated at 30˚C for 90 min followed by trimethylsilylation with N-methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA, 90 μL) containing C8–C30 fatty acid methyl esters (FAMEs) as internal standards by shaking at 37˚C for 30min.

Chromatography:

Chromatography ID:	CH002263
Chromatography Summary:	HILIC positive
Instrument Name:	Thermo Vanquish
Column Name:	Waters XBridge Amide (100 x 4.6mm,3.5um)
Chromatography Type:	HILIC

Chromatography ID:	CH002264
Chromatography Summary:	HILIC negative
Instrument Name:	Thermo Vanquish
Column Name:	Waters XBridge Amide (100 x 4.6mm,3.5um)
Chromatography Type:	HILIC

Chromatography ID:	CH002265
Chromatography Summary:	CSH positive
Instrument Name:	Thermo Vanquish
Column Name:	Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Chromatography Type:	Reversed phase

Chromatography ID:	CH002266
Chromatography Summary:	CSH negative
Instrument Name:	Thermo Vanquish
Column Name:	Waters Acquity CSH C18 (100 x 2.1mm,1.7um)
Chromatography Type:	Reversed phase

Chromatography ID:	CH002267
Chromatography Summary:	GC
Instrument Name:	Agilent 6890N
Column Name:	Restek Rtx-5Sil (30m x 0.25mm,0.25um)
Chromatography Type:	GC

Analysis:

Analysis ID:	AN003057
Analysis Type:	MS
Chromatography ID:	CH002263
Num Factors:	21
Num Metabolites:	238
Rt Units:	Minutes
Units:	Peak height

Analysis ID:	AN003058
Analysis Type:	MS
Chromatography ID:	CH002264
Num Factors:	21
Num Metabolites:	163
Rt Units:	Minutes
Units:	Peak height

Analysis ID:	AN003059
Analysis Type:	MS
Chromatography ID:	CH002265
Num Factors:	21
Num Metabolites:	700
Rt Units:	Minutes
Units:	Peak height

Analysis ID:	AN003060
Analysis Type:	MS
Chromatography ID:	CH002266
Num Factors:	21
Num Metabolites:	323
Rt Units:	Minutes
Units:	Peak height

Analysis ID:	AN003061
Analysis Type:	MS
Chromatography ID:	CH002267
Num Factors:	21
Num Metabolites:	123
Units:	Peak height