ArticleBiological psychiatry2022
Sex-Specific Role for SLIT1 in Regulating Stress Susceptibility.
Article in Biological psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- A female-specific role for Slit1 in prenatal stress-induced depression vulnerability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Semaphorin 3A-mediated perineuronal nets formation incubates depressive-like behaviors in male mice via activating parvalbumin-expressing interneurons.Molecular psychiatry · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- mPFC Synaptosome Proteomics Reveals Novel Pathways and Muscarinic Receptor Changes in a Learned Helplessness Mouse Model.bioRxiv : the preprint server for biology · 2026Article
- Structural variant landscape provides insights into genome organisation and domestication in European seabass.BMC biology · 2025Article
- Novel Insights into Changes in Gene Expression within the Hypothalamus in Two Asthma Mouse Models: A Transcriptomic Lung-Brain Axis Study.International journal of molecular sciences · 2024Article
- Cortical-brainstem circuitry attenuates physiological stress reactivity.The Journal of physiology · 2024Article
- A zinc finger transcription factor enables social behaviors while controlling transposable elements and immune response in prefrontal cortex.Translational psychiatry · 2024Article
- Gains and Losses: Resilience to Social Defeat Stress in Adolescent Female Mice.Biological psychiatry · 2024Article
- Sex Differences in Stress Response: Classical Mechanisms and Beyond.Current neuropharmacology · 2024Article
- Divergent single cell transcriptome and epigenome alterations in ALS and FTD patients with C9orf72 mutation.Nature communications · 2023Article
- Neuronal guidance genes in health and diseases.Protein & cell · 2023Review
- Regulation of axon pathfinding by astroglia across genetic model organisms.Frontiers in cellular neuroscience · 2023Review
- Awakening the dormant: Role of axonal guidance cues in stress-induced reorganization of the adult prefrontal cortex leading to depression-like behavior.Frontiers in neural circuits · 2023Review
- Introduction to Special Issue: Insight Into Sex Differences in Neuropsychiatric Syndromes From Transcriptomic Analyses.Biological psychiatry · 2022Article
Corrections and comments
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Authors and funding
22 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMajor depressive disorder is a pervasive and debilitating syndrome characterized by mood disturbances, anhedonia, and alterations in cognition. While the prevalence of major depressive disorder is twice as high for women as men, little is known about the molecular mechanisms that drive sex differences in depression susceptibility.
methodsWe discovered that SLIT1, a secreted protein essential for axonal navigation and molecular guidance during development, is downregulated in the adult ventromedial prefrontal cortex (vmPFC) of women with depression compared with healthy control subjects, but not in men with depression. This sex-specific downregulation of Slit1 was also observed in the vmPFC of mice exposed to chronic variable stress. To identify a causal, sex-specific role for SLIT1 in depression-related behavioral abnormalities, we performed knockdown (KD) of Slit1 expression in the vmPFC of male and female mice.
resultsWhen combined with stress exposure, vmPFC Slit1 KD reflected the human condition by inducing a sex-specific increase in anxiety- and depression-related behaviors. Furthermore, we found that vmPFC Slit1 KD decreased the dendritic arborization of vmPFC pyramidal neurons and decreased the excitability of the neurons in female mice, effects not observed in males. RNA sequencing analysis of the vmPFC after Slit1 KD in female mice revealed an augmented transcriptional stress signature.
conclusionsTogether, our findings establish a crucial role for SLIT1 in regulating neurophysiological and transcriptional responses to stress within the female vmPFC and provide mechanistic insight into novel signaling pathways and molecular factors influencing sex differences in depression susceptibility.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.