ArticleProceedings of the National Academy of Sciences of the United States of America2012
3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.Frontiers in pharmacology · 2022Pooled it
- A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Trial
- An exploration of the relationships between the effects of psilocybin on behavior, 5-HTJournal of psychopharmacology (Oxford, England) · 2026Article
- Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis.Journal of neuroinflammation · 2025Article
- Single cell resolution of neurosteroidogenesis in the murine brain: intermediary biosynthesis.The Journal of endocrinology · 2025Article
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Behavioral benefits of GSK-3β inhibition and state-dependent microtubule signatures in theFrontiers in neuroscience · 2025Article
- Structural basis of binding the unique N-terminal domain of microtubule-associated protein 2c to proteins regulating kinases of signaling pathways.The Journal of biological chemistry · 2024Article
- Neurosteroids: mechanistic considerations and clinical prospects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Chronic MAP4343 reverses escalated alcohol drinking in a mouse model of alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- A synthetic pregnenolone analog promotes microtubule dynamics and neural development.Cell & bioscience · 2022Article
- The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids.Microbiome · 2022Article
- Therapeutic potential of pregnenolone and pregnenolone methyl ether on depressive and CDKL5 deficiency disorders: Focus on microtubule targeting.Journal of neuroendocrinology · 2022Review
- Paracetamol (acetaminophen) rescues cognitive decline, neuroinflammation and cytoskeletal alterations in a model of post-operative cognitive decline (POCD) in middle-aged rats.Scientific reports · 2021Article
- Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond.Neurobiology of stress · 2019Article
- Microtubules: A Key to Understand and Correct Neuronal Defects in CDKL5 Deficiency Disorder?International journal of molecular sciences · 2019Review
- Structure and Functions of Microtubule Associated Proteins Tau and MAP2c: Similarities and Differences.Biomolecules · 2019Review
- Disruption of lipid-raft localized GαNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Steroids and Brain, a Rising Bio-Medical Domain: a Perspective.Frontiers in endocrinology · 2018Article
- Gender-Related Hippocampal Proteomics Study from Young Rats After Chronic Unpredicted Mild Stress Exposure.Molecular neurobiology · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in α-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of α-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naïve Sprague-Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering "depressive-like" behaviors. These effects were accompanied by modifications of α-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action.
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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.