Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice
Abstract The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined the association between multiple features of mitochond...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39941-0 |
| _version_ | 1797558597053317120 |
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| author | Ayelet M. Rosenberg Manish Saggar Anna S. Monzel Jack Devine Peter Rogu Aaron Limoges Alex Junker Carmen Sandi Eugene V. Mosharov Dani Dumitriu Christoph Anacker Martin Picard |
| author_facet | Ayelet M. Rosenberg Manish Saggar Anna S. Monzel Jack Devine Peter Rogu Aaron Limoges Alex Junker Carmen Sandi Eugene V. Mosharov Dani Dumitriu Christoph Anacker Martin Picard |
| author_sort | Ayelet M. Rosenberg |
| collection | DOAJ |
| description | Abstract The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in male mice with diverse behavioral phenotypes. Miniaturized assays of mitochondrial respiratory chain enzyme activities and mitochondrial DNA (mtDNA) content were deployed on 571 samples across 17 brain areas, defining specific patterns of mito-behavior associations. By applying multi-slice network analysis to our brain-wide mitochondrial dataset, we identified three large-scale networks of brain areas with shared mitochondrial signatures. A major network composed of cortico-striatal areas exhibited the strongest mitochondria-behavior correlations, accounting for up to 50% of animal-to-animal behavioral differences, suggesting that this mito-based network is functionally significant. The mito-based brain networks also overlapped with regional gene expression and structural connectivity, and exhibited distinct molecular mitochondrial phenotype signatures. This work provides convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct, behaviorally-relevant mitochondrial phenotypes exist across the male mouse brain. |
| first_indexed | 2024-03-10T17:32:45Z |
| format | Article |
| id | doaj.art-941e18427e5a4b75b3dce7e14eca5d2e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:32:45Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-941e18427e5a4b75b3dce7e14eca5d2e2023-11-20T09:57:18ZengNature PortfolioNature Communications2041-17232023-08-0114111910.1038/s41467-023-39941-0Brain mitochondrial diversity and network organization predict anxiety-like behavior in male miceAyelet M. Rosenberg0Manish Saggar1Anna S. Monzel2Jack Devine3Peter Rogu4Aaron Limoges5Alex Junker6Carmen Sandi7Eugene V. Mosharov8Dani Dumitriu9Christoph Anacker10Martin Picard11Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical CenterDepartment of Psychiatry and Behavioral Sciences, Stanford UniversityDivision of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical CenterDivision of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical CenterColumbia University Institute for Developmental Sciences, Department of Psychiatry, Columbia University Irving Medical CenterDepartment of Biological Sciences, Columbia UniversityDivision of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical CenterBrain Mind Institute, Ecole Polytechnique Federal de Lausanne (EPFL)Division of Molecular Therapeutics, Department of Psychiatry, Columbia University Irving Medical CenterColumbia University Institute for Developmental Sciences, Department of Psychiatry, Columbia University Irving Medical CenterColumbia University Institute for Developmental Sciences, Department of Psychiatry, Columbia University Irving Medical CenterDivision of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical CenterAbstract The brain and behavior are under energetic constraints, limited by mitochondrial energy transformation capacity. However, the mitochondria-behavior relationship has not been systematically studied at a brain-wide scale. Here we examined the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in male mice with diverse behavioral phenotypes. Miniaturized assays of mitochondrial respiratory chain enzyme activities and mitochondrial DNA (mtDNA) content were deployed on 571 samples across 17 brain areas, defining specific patterns of mito-behavior associations. By applying multi-slice network analysis to our brain-wide mitochondrial dataset, we identified three large-scale networks of brain areas with shared mitochondrial signatures. A major network composed of cortico-striatal areas exhibited the strongest mitochondria-behavior correlations, accounting for up to 50% of animal-to-animal behavioral differences, suggesting that this mito-based network is functionally significant. The mito-based brain networks also overlapped with regional gene expression and structural connectivity, and exhibited distinct molecular mitochondrial phenotype signatures. This work provides convergent multimodal evidence anchored in enzyme activities, gene expression, and animal behavior that distinct, behaviorally-relevant mitochondrial phenotypes exist across the male mouse brain.https://doi.org/10.1038/s41467-023-39941-0 |
| spellingShingle | Ayelet M. Rosenberg Manish Saggar Anna S. Monzel Jack Devine Peter Rogu Aaron Limoges Alex Junker Carmen Sandi Eugene V. Mosharov Dani Dumitriu Christoph Anacker Martin Picard Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice Nature Communications |
| title | Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice |
| title_full | Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice |
| title_fullStr | Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice |
| title_full_unstemmed | Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice |
| title_short | Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice |
| title_sort | brain mitochondrial diversity and network organization predict anxiety like behavior in male mice |
| url | https://doi.org/10.1038/s41467-023-39941-0 |
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