ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Upregulation of mGlu2 receptors via NF-κB p65 acetylation is involved in the Proneurogenic and antidepressant effects of acetyl-L-carnitine.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- Acetyl-l-carnitine deficiency in patients with major depressive disorder.Proceedings of the National Academy of Sciences of the United States of America · 2018Trial
- Acetyl-L-Carnitine in the Treatment of Peripheral Neuropathies: A Narrative Review.Pain and therapy · 2026Review
- Metabolomics Highlights Reduced Glutamate and Acetylcarnitine in the Amniotic Fluid of Cytomegalovirus-Infected Pregnant Women.Journal of proteome research · 2026Article
- The multifaceted role of ATM protein in neural stem/progenitor cell biology and neurogenesis: beyond DNA damage response.Frontiers in pharmacology · 2026Review
- Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.Molecular psychiatry · 2025Article
- Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.Translational psychiatry · 2025Article
- Multidimensional Effects of Stress on Neuronal Exosome Levels and Simultaneous Transcriptomic Profiles.Biological psychiatry global open science · 2025Article
- Neuropsychiatric Manifestations of COVID-19 Disease and Post COVID Syndrome: The Role of N-acetylcysteine and Acetyl-L-carnitine.Current neuropharmacology · 2025Review
- Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.Research square · 2024Article
- Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.medRxiv : the preprint server for health sciences · 2024Article
- The neuropsychopharmacology of acetyl-L-carnitine (LAC): basic, translational and therapeutic implications.Discover mental health · 2024Review
- The Pharmacological Treatment of Chronic Pain: From Guidelines to Daily Clinical Practice.Pharmaceutics · 2023Review
- Synergic action of L-acetylcarnitine and L-methylfolate in Mouse Models of Stress-Related Disorders and Human iPSC-Derived Dopaminergic Neurons.Frontiers in pharmacology · 2022Article
- Carnitine and Depression.Frontiers in nutrition · 2022Review
- Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology.International journal of molecular sciences · 2021Review
- βNeural regeneration research · 2021Article
- Insulin receptor substrate in brain-enriched exosomes in subjects with major depression: on the path of creation of biosignatures of central insulin resistance.Molecular psychiatry · 2021Article
- Regulation of Neurogenesis by Organic Cation Transporters: Potential Therapeutic Implications.Handbook of experimental pharmacology · 2021Article
- Non-targeted Metabolomics Profiling of Plasma Samples From Patients With Major Depressive Disorder.Frontiers in psychiatry · 2021Article
- L-Carnitine and Acetyl-L-Carnitine: Potential Novel Biomarkers for Major Depressive Disorder.Frontiers in psychiatry · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-κB p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-κB pathway, and in particular by p65 acetylation, and subsequent NF-κB-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressants.
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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.