ArticleFrontiers in molecular neuroscience2011
GSK-3 as a Target for Lithium-Induced Neuroprotection Against Excitotoxicity in Neuronal Cultures and Animal Models of Ischemic Stroke.
Article in Frontiers in molecular neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis.European child & adolescent psychiatry · 2018Pooled it
- Lithium Chloride-Induced Nuclear Envelope Remodeling in 3D Endometrial Cancer Spheroids.International journal of molecular sciences · 2026Article
- BDNF and GSK-3β signaling in depression: molecular mechanisms underlying neural plasticity dysfunction.Molecular biology reports · 2026Review
- Genetic predictors of lithium response in an ethiopian cohort of patients with bipolar disorder.Annals of general psychiatry · 2026Article
- Network-based analysis identifies shared mechanisms between ischemic stroke and myocardial infarction and therapeutic ingredients of Buyang Huanwu Decoction.Frontiers in genetics · 2026Article
- Role of GSK-3 Inhibition in Alzheimer's Disease Therapy.Current Alzheimer research · 2026Review
- Protective effects of low-dose lithium treatment on rat postural muscle under conditions of disuse.Pflugers Archiv : European journal of physiology · 2025Article
- Innovative approaches for the treatment of stroke: a recent update.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3β/p-CREB/BDNF Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Targeting intracellular autophagic process for the treatment of post-stroke ischemia/reperfusion injury.Animal models and experimental medicine · 2025Review
- Promising tools into oxidative stress: A review of non-rodent model organisms.Redox biology · 2024Review
- The Role of Glycogen Synthase Kinase-3β in the Zinc-Mediated Neuroprotective Effect of Metformin in Rats with Glutamate Neurotoxicity.Biological trace element research · 2024Article
- Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review.International journal of medical sciences · 2024Review
- Mechanistic Implications of GSK and CREB Crosstalk in Ischemia Injury.Neurotoxicity research · 2023Review
- Oleuropein confers neuroprotection against rotenone-induced model of Parkinson's disease via BDNF/CREB/Akt pathway.Scientific reports · 2023Article
- Article
- Beyond its Psychiatric Use: The Benefits of Low-dose Lithium Supplementation.Current neuropharmacology · 2023Review
- Imipramine Can Be Effective on Depressive-Like Behaviors, but Not on Neurotrophic Factor Levels in an Animal Model for Bipolar Disorder Induced by Ouabain.Molecular neurobiology · 2022Article
- Lithium Biological Action Mechanisms after Ischemic Stroke.Life (Basel, Switzerland) · 2022Review
- Adenosine AMolecular neurobiology · 2022Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mood stabilizer lithium inhibits glycogen synthase kinase-3 (GSK-3) directly or indirectly by enhancing serine phosphorylation of both α and β isoforms. Lithium robustly protected primary brain neurons from glutamate-induced excitotoxicity; these actions were mimicked by other GSK-3 inhibitors or silencing/inhibiting GSK-3α and/or β isoforms. Lithium rapidly activated Akt to enhance GSK-3 serine phosphorylation and to block glutamate-induced Akt inactivation. Lithium also up-regulated Bcl-2 and suppressed glutamate-induced p53 and Bax. Induction of brain-derived neurotrophic factor (BDNF) was required for lithium's neuroprotection to occur. BDNF promoter IV was activated by GSK-3 inhibition using lithium or other drugs, or through gene silencing/inactivation of either isoform. Further, lithium's neuroprotective effects were associated with inhibition of NMDA receptor-mediated calcium influx and down-stream signaling. In rodent ischemic models, post-insult treatment with lithium decreased infarct volume, ameliorated neurological deficits, and improved functional recovery. Up-regulation of heat-shock protein 70 and Bcl-2 as well as down-regulation of p53 likely contributed to lithium's protective effects. Delayed treatment with lithium improved functional MRI responses, which was accompanied by enhanced angiogenesis. Two GSK-3-regulated pro-angiogenic factors, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor were induced by lithium. Finally, lithium promoted migration of mesenchymal stem cells (MSCs) by up-regulation of MMP-9 through GSK-3β inhibition. Notably, transplantation of lithium-primed MSCs into ischemic rats enhanced MSC migration to the injured brain regions and improved the neurological performance. Several other GSK-3 inhibitors have also been reported to be beneficial in rodent ischemic models. Together, GSK-3 inhibition is a rational strategy to combat ischemic stroke and other excitotoxicity-related brain disorders.
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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.