Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation
The metabolic mechanisms underlying the formation of early-life episodic memories remain poorly characterized. Here, we assessed the metabolomic profile of the rat hippocampus at different developmental ages both at baseline and following episodic learning. We report that the hippocampal metabolome...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:0465be4af6d54d64acf1da9a14ec6e982021-11-26T11:10:23ZMetabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation10.7554/eLife.685902050-084Xe68590https://doaj.org/article/0465be4af6d54d64acf1da9a14ec6e982021-11-01T00:00:00Zhttps://elifesciences.org/articles/68590https://doaj.org/toc/2050-084XThe metabolic mechanisms underlying the formation of early-life episodic memories remain poorly characterized. Here, we assessed the metabolomic profile of the rat hippocampus at different developmental ages both at baseline and following episodic learning. We report that the hippocampal metabolome significantly changes over developmental ages and that learning regulates differential arrays of metabolites according to age. The infant hippocampus had the largest number of significant changes following learning, with downregulation of 54 metabolites. Of those, a large proportion was associated with the glutathione-mediated cellular defenses against oxidative stress. Further biochemical, molecular, and behavioral assessments revealed that infantile learning evokes a rapid and persistent increase in the activity of neuronal glutathione reductase, the enzyme that regenerates reduced glutathione from its oxidized form. Inhibition of glutathione reductase selectively impaired long-term memory formation in infant but not in juvenile and adult rats, confirming its age-specific role. Thus, metabolomic profiling revealed that the hippocampal glutathione-mediated antioxidant pathway is differentially required for the formation of infantile memory.Benjamin BessièresEmmanuel CruzCristina M AlberinieLife Sciences Publications Ltdarticlemetabolomehippocampusepisodic learningbrain developmentglutathioneMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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metabolome hippocampus episodic learning brain development glutathione Medicine R Science Q Biology (General) QH301-705.5 |
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metabolome hippocampus episodic learning brain development glutathione Medicine R Science Q Biology (General) QH301-705.5 Benjamin Bessières Emmanuel Cruz Cristina M Alberini Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation |
| description |
The metabolic mechanisms underlying the formation of early-life episodic memories remain poorly characterized. Here, we assessed the metabolomic profile of the rat hippocampus at different developmental ages both at baseline and following episodic learning. We report that the hippocampal metabolome significantly changes over developmental ages and that learning regulates differential arrays of metabolites according to age. The infant hippocampus had the largest number of significant changes following learning, with downregulation of 54 metabolites. Of those, a large proportion was associated with the glutathione-mediated cellular defenses against oxidative stress. Further biochemical, molecular, and behavioral assessments revealed that infantile learning evokes a rapid and persistent increase in the activity of neuronal glutathione reductase, the enzyme that regenerates reduced glutathione from its oxidized form. Inhibition of glutathione reductase selectively impaired long-term memory formation in infant but not in juvenile and adult rats, confirming its age-specific role. Thus, metabolomic profiling revealed that the hippocampal glutathione-mediated antioxidant pathway is differentially required for the formation of infantile memory. |
| format |
article |
| author |
Benjamin Bessières Emmanuel Cruz Cristina M Alberini |
| author_facet |
Benjamin Bessières Emmanuel Cruz Cristina M Alberini |
| author_sort |
Benjamin Bessières |
| title |
Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation |
| title_short |
Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation |
| title_full |
Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation |
| title_fullStr |
Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation |
| title_full_unstemmed |
Metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation |
| title_sort |
metabolomic profiling reveals a differential role for hippocampal glutathione reductase in infantile memory formation |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/0465be4af6d54d64acf1da9a14ec6e98 |
| work_keys_str_mv |
AT benjaminbessieres metabolomicprofilingrevealsadifferentialroleforhippocampalglutathionereductaseininfantilememoryformation AT emmanuelcruz metabolomicprofilingrevealsadifferentialroleforhippocampalglutathionereductaseininfantilememoryformation AT cristinamalberini metabolomicprofilingrevealsadifferentialroleforhippocampalglutathionereductaseininfantilememoryformation |
| _version_ |
1718409515157684224 |