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Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression

Harvard Dataverse (Africa Rice Center, Bioversity International, CCAFS, CIAT, IFPRI, IRRI and WorldFish)

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Title Astrocyte dysfunction drives abnormal resting-state functional connectivity in depression
 
Identifier https://doi.org/10.7910/DVN/YBKBZF
 
Creator Liu, Jiaming
 
Publisher Harvard Dataverse
 
Description Major depressive disorder (MDD) is a devastating mental disorder that affects up to 17% of the population worldwide. Even though brain-wide network-level abnormalities in MDD patients via resting-state functional MRI (rsfMRI) exist, the mechanisms underlying such network changes are unknown despite their immense potential for depression diagnosis and management. Here, we show that the astrocytic calcium deficient mice, inositol 1,4,5-trisphosphate-type-2 receptor knockout mice (Itpr2-/- mice), display abnormal rsfMRI functional connectivity (rsFC) in depression-related networks, especially decreased rsFC in mPFC-related pathways. We further uncover rsFC decreases in MDD patients highly consistent with those of Itpr2-/- mice, especially in mPFC-related pathways. Optogenetic activation of mPFC astrocytes partially enhances rsFC in depression-related networks in both Itpr2-/- and wild-type mice. Optogenetic activation of the mPFC neurons or mPFC-striatum pathway rescues disrupted rsFC and depressive-like behaviors in Itpr2-/- mice. Our results identify the previously unknown role of astrocyte dysfunction in driving rsFC abnormalities in depression.
 
Subject Medicine, Health and Life Sciences
 
Contributor Liu, Jiaming