2025-07-11 マウントサイナイ医療システム(MSHS)
<関連情報>
- https://www.mountsinai.org/about/newsroom/2025/mount-sinai-researchers-uncover-differences-in-how-males-and-females-change-their-mind-when-reflecting-on-past-mistakes
- https://www.science.org/doi/10.1126/sciadv.adr3228
- https://www.cell.com/neuron/fulltext/S0896-6273(20)30230-0
神経経済的意思決定はLINC00473によって性差に依存して前頭前皮質内側で調節される Change-of-mind neuroeconomic decision-making is modulated by LINC00473 in medial prefrontal cortex in a sex-dependent manner
Romain Durand-de Cuttoli, Orna Issler, Samantha M. B. Pedersen, Benjamin Yakubov, […] , and Brian M. Sweis
Science Advances Published:11 Jul 2025
DOI:https://doi.org/10.1126/sciadv.adr3228
Abstract
Changing one’s mind involves reappraisals between past costs versus future value and may be altered in psychopathology. Long intergenic noncoding RNA LINC00473 in medial prefrontal cortex (mPFC) can induce stress resilience in a sex-dependent manner, but its role in cognition is unknown. We characterized decision-making behavior in male and female mice in the neuroeconomic paradigm Restaurant Row following virus-mediated expression of LINC00473 in mPFC. Mice foraged for food among varying temporal costs and subjective value while on a limited time budget. Without affecting primary deliberative decisions, LINC00473 selectively influenced re-evaluative choices in a sex-dependent manner. This included changing how mice (i) cached value with the passage of time and (ii) weighed prior mistakes, which underlie the computational bases of sensitivity to sunk costs and regret. These findings suggest that a common value function is shared between these neuroeconomic processes and reveal a bridge between molecular drivers of stress resilience and psychological mechanisms underlying sex-specific proclivities in negative rumination.
うつ病におけるロングノンコーディングRNA LINC00473の性特異的役割 Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression
Orna Issler ∙ Yentl Y. van der Zee ∙ Aarthi Ramakrishnan ∙ … ∙ Yan Dong ∙ Li Shen ∙ Eric J. Nestler
Neuron Published:April 17, 2020
DOI:https://doi.org/10.1016/j.neuron.2020.03.023
Highlights
- LncRNAs are robustly altered in depression in a sex- and brain site-specific manner
- LINC00473 is downregulated in cortex of depressed females but not males
- LINC00473 expression in mouse cortex promotes stress resilience in females only
- LINC00473 regulates gene expression and physiology in a sex-specific manner
Summary
Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene LINC00473 as downregulated in prefrontal cortex (PFC) of depressed females but not males. Using viral-mediated gene transfer to express LINC00473 in adult mouse PFC neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates LINC00473 as a CREB effector. Together, our studies identify LINC00473 as a female-specific driver of stress resilience that is aberrant in female depression.
