RT Journal Article
SR Electronic
T1 A Network Approach to Mapping Mouse Brain-wide Mitochondrial Respiratory Chain Capacity in Relation to Behavior
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.02.446767
DO 10.1101/2021.06.02.446767
A1 Ayelet M Rosenberg
A1 Manish Saggar
A1 Peter Rogu
A1 Aaron Limoges
A1 Alex Junker
A1 Carmen Sandi
A1 Eugene V. Mosharov
A1 Dani Dumitriu
A1 Christoph Anacker
A1 Martin Picard
YR 2022
UL http://biorxiv.org/content/early/2022/08/03/2021.06.02.446767.abstract
AB The brain and behavior are under energetic constraints, limited by mitochondrial energy production capacity. However, the mitochondria-behavior relationship has not been systematically studied on a brain-wide scale. Here we examine the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in 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 regions, defining specific patterns of mito-behavior associations that vary across brain regions and behaviors. Furthermore, multi-slice network analysis applied to our brain-wide mitochondrial dataset identified three large-scale networks of brain regions with shared mitochondrial signatures. A major network composed of cortico-striatal regions exhibited the strongest mitochondria-behavior correlations, suggesting that this mito-based network is functionally significant. Mito-based networks also overlap with regional gene expression and structural connectivity, thereby providing convergent multimodal evidence of mitochondrial respiratory chain functional organization anchored in gene, brain and behavior.Competing Interest StatementThe authors declare no competing interest related to this work. M.P. has consulted and received funding from Epirium Bio. C.A. receives research funding from Sunovion Pharmaceuticals.