Orna Issler, Yentl Y van der Zee, Aarthi Ramakrishnan, Sunhui Xia, Alexander K Zinsmaier, Chunfeng Tan, Wei Li, Caleb J Browne, Deena M Walker, Marine Salery, Angélica Torres-Berrío, Rita Futamura, Julia E Duffy, Benoit Labonte, Matthew J Girgenti, Carol A Tamminga, Jeffrey L Dupree, Yan Dong, James W Murrough, Li Shen, Eric J Nestler
Women suffer from depression at twice the rate of men, but the underlying molecular mechanisms are poorly understood. Here, we identify marked baseline sex differences in the expression of long noncoding RNAs (lncRNAs), a class of regulatory transcripts, in human postmortem brain tissue that are profoundly lost in depression. One such human lncRNA, RP11-298D21.1 (which we termed FEDORA), is enriched in oligodendrocytes and neurons and up-regulated in the prefrontal cortex (PFC) of depressed females only. We found that virally expressing FEDORA selectively either in neurons or in oligodendrocytes of PFC promoted depression-like behavioral abnormalities in female mice only, changes associated with cell type-specific regulation of synaptic properties, myelin thickness, and gene expression...
December 2, 2022: Science Advances