ArticleNeurotoxicology2018
Valproic acid attenuates manganese-induced reduction in expression of GLT-1 and GLAST with concomitant changes in murine dopaminergic neurotoxicity.
Article in Neurotoxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Differential impact of manganese on glutamate clearance, electroencephalography, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Impact of air pollution and occupational inhalation exposures on neurodegenerative disorders: An epigenetic perspective.iScience · 2025Review
- Nano-mediated Management of Metal Toxicity-induced Neurodegeneration: A Critical Review.Molecular neurobiology · 2025Review
- The Role of Epigenetics in Manganese Neurotoxicity: An Update with a Focus on Non-Coding RNAs and Histone Modifications.Neurochemical research · 2025Review
- Yin Yang 1: Function, Mechanisms, and Glia.Neurochemical research · 2025Review
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- CYP1B1 affects the integrity of the blood-brain barrier and oxidative stress in the striatum: An investigation of manganese-induced neurotoxicity.CNS neuroscience & therapeutics · 2024Article
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Transient plasticity response is regulated by histone deacetylase inhibitor in oxygen-glucose deprivation condition.Pharmacological reports : PR · 2023Article
- Beneficial role of rosemary extract on oxidative stress-mediated neuronal apoptosis in rotenone-induced attention deficit hyperactivity disease in juvenile rat model.Acta bio-medica : Atenei Parmensis · 2023Article
- Acute manganese exposure impairs glutamatergic function in a young mouse model of Alzheimer's disease.Neurotoxicology · 2023Article
- Article
- Astrocyte regulation of synaptic signaling in psychiatric disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Review
- Testing the extreme male hypothesis in the valproate mouse model; sex-specific effects on plasma testosterone levels and tyrosine hydroxylase expression in the anteroventral periventricular nucleus, but not on parental behavior.Frontiers in behavioral neuroscience · 2023Article
- Current insights in the molecular genetic pathogenesis of amyotrophic lateral sclerosis.Frontiers in neuroscience · 2023Review
- Article
- Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson's Disease Pathogenesis: A Narrative Review.Brain sciences · 2022Review
- Mechanisms of manganese-induced neurotoxicity and the pursuit of neurotherapeutic strategies.Frontiers in pharmacology · 2022Review
- Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.International journal of molecular sciences · 2021Review
- Critical Involvement of Glial Cells in Manganese Neurotoxicity.BioMed research international · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models. The results showed that VPA increased promoter activity, mRNA/protein levels of GLAST/GLT-1 and glutamate uptake, and reversed Mn-reduced GLAST/GLT-1 in in vitro astrocyte cultures. VPA also attenuated Mn-induced reduction of GLAST and GLT-1 mRNA/protein levels in midbrain and striatal regions of the mouse brain when VPA (200 mg/kg, i.p., daily, 21 d) was administered 30 min prior to Mn exposure (30 mg/kg, intranasal instillation, daily, 21 d). Importantly, VPA attenuated Mn-induced dopaminergic neuronal damage by reversing Mn-induced decrease of tyrosine hydroxylase (TH) mRNA/protein levels in the nigrostriatal regions. VPA also reversed Mn-induced reduction of histone acetylation in astrocytes as well as mouse brain tissue. Taken together, VPA exerts attenuation against Mn-induced decrease of astrocytic glutamate transporters parallel with reversing Mn-induced dopaminergic neurotoxicity and Mn-reduced histone acetylation. Our findings suggest that VPA could serve as a potential neuroprotectant against Mn neurotoxicity as well as other neurodegenerative diseases associated with excitotoxicity and impaired astrocytic glutamate transporters.
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Registered trials
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