ArticleThe international journal of neuropsychopharmacology2013
Neuroprotective effects of the mood stabilizer lamotrigine against glutamate excitotoxicity: roles of chromatin remodelling and Bcl-2 induction.
Article in The international journal of neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Glutamatergic Medications for Obsessive-Compulsive and Related Disorders: A Systematic Review and Meta-Analysis.JAMA network open · 2025Pooled it
- Dissecting the Epigenetic Changes Induced by Non-Antipsychotic Mood Stabilizers on Schizophrenia and Affective Disorders: A Systematic Review.Frontiers in pharmacology · 2020Pooled it
- Lithium partially rescues gene expression and enhancer activity from heterozygous knockout of AKAP11 while inducing novel differential changes.Scientific reports · 2025Article
- Epigenetics and Gut Microbiota in the Pathogenesis and Treatment of Bipolar Disorder (BD).Cells · 2025Review
- Review
- Underlying biological mechanisms of emotion dysregulation in bipolar disorder.Frontiers in psychiatry · 2025Review
- Drugs with glutamate-based mechanisms of action in psychiatry.Pharmacological reports : PR · 2024Review
- Neuroprotective Properties of Antiepileptics: What are the Implications for Psychiatric Disorders?Current medicinal chemistry · 2024Review
- Understanding Lamotrigine's Role in the CNS and Possible Future Evolution.International journal of molecular sciences · 2023Review
- Involvement of a BH3-only apoptosis sensitizer gene Blm-s in hippocampus-mediated mood control.Translational psychiatry · 2022Article
- From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.Cancers · 2022Review
- Article
- In vivo human brain expression of histone deacetylases in bipolar disorder.Translational psychiatry · 2020Article
- Investigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder.Journal of experimental pharmacology · 2020Review
- Brain targeting stealth lipomers of combined antiepileptic-anti-inflammatory drugs as alternative therapy for conventional anti-Parkinson's.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Complex Combination Pharmacotherapy for Bipolar Disorder: Knowing When Less Is More or More Is Better.Focus (American Psychiatric Publishing) · 2019Review
- Type A monoamine oxidase and serotonin are coordinately involved in depressive disorders: from neurotransmitter imbalance to impaired neurogenesis.Journal of neural transmission (Vienna, Austria : 1996) · 2018Review
- Glutamate-Modulating Drugs as a Potential Therapeutic Strategy in Obsessive-Compulsive Disorder.Current neuropharmacology · 2017Review
- Valproic Acid and Other HDAC Inhibitors Upregulate FGF21 Gene Expression and Promote Process Elongation in Glia by Inhibiting HDAC2 and 3.The international journal of neuropsychopharmacology · 2016Article
- Neuroprotection as a Potential Therapeutic Perspective in Neurodegenerative Diseases: Focus on Antiepileptic Drugs.Neurochemical research · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Lamotrigine (LTG), a phenyltriazine derivative and anti-epileptic drug, has emerged as an effective first-line treatment for bipolar mood disorder. Like the other mood stabilizers lithium and valproate, LTG also has neuroprotective properties but its exact mechanisms remain poorly defined. The present study utilized rat cerebellar granule cells (CGCs) to examine the neuroprotective effects of LTG against glutamate-induced excitotoxicity and to investigate potential underlying mechanisms. CGCs pretreated with LTG were challenged with an excitotoxic dose of glutamate. Pretreatment caused a time- and concentration-dependent inhibition of glutamate excitotoxicity with nearly full protection at higher doses (≥ 100 μm), as revealed by cell viability assays and morphology. LTG treatment increased levels of acetylated histone H3 and H4 as well as dose- and time-dependently enhanced B-cell lymphoma-2 (Bcl-2) mRNA and protein levels; these changes were associated with up-regulation of the histone acetylation and activity of the Bcl-2 promoter. Importantly, lentiviral-mediated Bcl-2 silencing by shRNA reduced both LTG-induced Bcl-2 mRNA up-regulation and neuroprotection against glutamate excitotoxicity. Finally, the co-presence of a sub-effective concentration of LTG (10 μm) with lithium or valproate produced synergistic neuroprotection. Together, our results demonstrate that the neuroprotective effects of LTG against glutamate excitotoxicity likely involve histone deacetylase inhibition and downstream up-regulation of anti-apoptotic protein Bcl-2. These underlying mechanisms may contribute to the clinical efficacy of LTG in treating bipolar disorder and warrant further investigation.
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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.