ArticleBiological psychiatry2023
Impaired Endogenous Neurosteroid Signaling Contributes to Behavioral Deficits Associated With Chronic Stress.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Peripartum allopregnanolone blood concentrations and depressive symptoms: a systematic review and individual participant data meta-analysis.Molecular psychiatry · 2025Pooled it
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Neurosteroid-Mediated Neuroprotection via mTORC1/AMPK/BDNF Signaling Pathway in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Multiplexed changes in synaptic transmission underlie stress-induced reduction of persistent firing in the parietal cortex.Progress in neurobiology · 2026Article
- Chronic stress enhances threat responding and impacts fear extinction.Learning & memory (Cold Spring Harbor, N.Y.) · 2026Article
- Maternal Sucrose Intake during Pregnancy Alone Disrupts Testosterone and Allopregnanolone Levels in the Fetal Brain of Rats.The Journal of nutrition · 2026Article
- Impact of impaired endogenous neurosteroidogenesis on outcomes following chronic alcohol exposure.bioRxiv : the preprint server for biology · 2026Article
- Rapid-acting NMDA and GABAergic Modulators in Mood Disorders: From Synaptic Mechanisms to Clinical Practice.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Review
- Molecular mechanisms of neurosteroids in temporal lobe epilepsy: current insights and therapeutic perspectives.Molecular biology reports · 2025Review
- Unravelling the multifaceted actions of neurosteroids: Machine learning and in vitro screening for novel target discovery.British journal of pharmacology · 2025Article
- Sex differences in resilience at puberty depend upon divergent effects of a stress steroid at α4βδ GABABrain research · 2025Article
- Neuroactive Steroids as Novel Promising Drugs in Therapy of Postpartum Depression-Focus on Zuranolone.International journal of molecular sciences · 2025Review
- Effects of early life stress on network and behavioral states.Psychoneuroendocrinology · 2025Article
- Neuroactive steroids and the pathophysiology of PTSD: Biomarkers for treatment targeting.Neuroscience and biobehavioral reviews · 2025Review
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Biased Information Routing Through the Basolateral Amygdala, Altered Valence Processing, and Impaired Affective States Associated With Psychiatric Illnesses.Biological psychiatry · 2025Review
- Early life stress influences epilepsy outcomes in mice.Epilepsy & behavior : E&B · 2025Article
- Article
- Astrocytic BDNF Modulates Sensitivity to Stress-Induced Anxiety-Like Behaviors.Research (Washington, D.C.) · 2025Article
- Neurosteroid Modulation of Synaptic and Extrasynaptic GABABiomolecules · 2024Article
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundChronic stress is a major risk factor for psychiatric illnesses, including depression. However, the pathophysiological mechanisms whereby stress leads to mood disorders remain unclear. Allopregnanolone acts as a positive allosteric modulator preferentially on δ subunit-containing GABA
methodsWe utilized a chronic unpredictable stress (CUS) mouse model, followed by behavioral and biochemical assays, to examine whether altered neurosteroid signaling contributes to behavioral outcomes following CUS. We subsequently performed in vivo CRISPR (clustered regularly interspaced short palindromic repeats) knockdown of rate-limiting enzymes involved in allopregnanolone synthesis, 5α-reductase type 1 and 2 (5α1/2), in addition to lentiviral overexpression of 5α1/2 in the basolateral amygdala (BLA) of mice that underwent CUS to assess the impact of 5α1/2 on behavioral outcomes.
resultsThe expression of δ subunit-containing GABA
conclusionsOur findings demonstrate that chronic stress impairs endogenous neurosteroid signaling in the BLA, which is sufficient to induce behavioral deficits. Further, these studies suggest that allopregnanolone-based treatments may directly target the underlying pathophysiology of mood disorders suggesting that targeting endogenous neurosteroidogenesis may offer a novel therapeutic strategy.
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Registered trials
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.