Dataset Information

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 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.

SUBMITTER: Rosenberg AM

PROVIDER: S-EPMC10415311 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice.

Rosenberg Ayelet M AM Saggar Manish M Monzel Anna S AS Devine Jack J Rogu Peter P Limoges Aaron A Junker Alex A Sandi Carmen C Mosharov Eugene V EV Dumitriu Dani D Anacker Christoph C Picard Martin M

Nature communications 20230810 1

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 (mtD ...[more]

PMID: 37563104

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Project description:IntroductionIn most mammals, paternal care is not mandatory for raising offspring. In house mice, experience with pups governs the extent and quality of paternal care. First-time fathers undergo a dramatic transition from ignoring or killing pups to caring for pups. The behavioral shift occurs together with changes in brain estrogen signaling as indicated by changes in estrogen receptor presence and distribution in multiple areas regulating olfaction, emotion, and motivation.MethodsWe measured changes in the expression of aromatase, the enzyme converting testosterone into estrogen, as an indirect measure of estrogen synthesis, in various areas of the limbic system in mice with increasing paternal experience.ResultsThe amount of paternal experience (5 or 27 days) was associated with increased numbers of immunocytochemically-identified aromatase expressing cells in the medial and cortical amygdala, posterior piriform cortex, and ventromedial hypothalamus. Functionally, these changes can be related to the disappearance of aggression or neglect towards pups when first-time fathers or, even more, well-experienced fathers are handling their own pups. In the lateral septum, the anterior piriform cortex and to some extent in the medial preoptic area, parental experience increased the number of aromatase-positive cells only in fathers with 27 days of experience, and only in the right hemisphere. This represents a novel case of brain-functional lateralization triggered by experience. Nuclei/areas associated with maternal care (medial preoptic area, bed nucleus of stria terminalis, nucleus accumbens) exhibited a left-hemisphere advantage in aromatase expressing cells, both in pup-naïve and pup-experienced males. This newly found lateralization may contribute to the left-hemisphere dominant processing and perception of pup calls to release parental behavior.ConclusionIn general, the experience-dependent changes in aromatase expression we observed in most brain areas did not mirror the previously reported changes in estrogen receptors (ERα) when pup-naïve males became pup-caring fathers. Hence, paternal behavior may depend, in a brain area-specific way, on the differential action of estrogen through its receptors and/or direct local modulation of neural processing.

Dataset Information

Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice.

Publications

Brain mitochondrial diversity and network organization predict anxiety-like behavior in male mice.

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