Targeting hyperphosphorylated tau with sodium selenate suppresses seizures in rodent models.
Open accessAbstract
Tau hyperphosphorylation has been implicated in the pathogenesis of a variety of forms of human epilepsy. Here we investigated whether treatment with sodium selenate, a drug which reduces pathological hyperphosphorylated tau by enhancement of PP2A activity, would inhibit seizures in rodent models. In vitro, sodium selenate reduced tau phosphorylation in human neuroblastoma cells and reversed the increase in tau phosphorylation induced by the PP2A inhibitor, okadaic acid. Sodium selenate treatment was then tested against three different rodent seizure models. Firstly the propensity of 6-Hz electrical corneal stimulation to induce seizures in adult mice was assessed following acute treatment with different doses of sodium selenate. Secondly, the number of seizures induced by pentylenetetrazole (PTZ) was quantified in rats following chronic sodium selenate treatment via drinking water. Finally, amygdala kindled rats were chronically treated with sodium selenate in drinking water and the length and the severity of the seizures evoked by stimulation of the amygdala recorded. The results demonstrated a dose-dependent protection of sodium selenate against 6-Hz stimulation induced seizures, and significant reduction in the total number of seizures following PTZ injection. Amygdala kindled rats chronically treated with sodium selenate had significantly shorter seizure duration compared controls, with more pronounced effects observed as the duration of treatment increased. The results…
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In animal models of temporal lobe epilepsy, tau hyperphosphorylation is observed in the amygdala, hippocampus, and cortex following chemical and electrical amygdala kindling.
“In animal models of TLE, tau hyperphosphorylation is observed in relevant brain regions, including the amygdala, hippocampus, and cortex, following chemical and electrical amygdala kindling (Jones et al., 2012; Liu et al., 2016; Alves et al., 2019).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Jones et al., 2012
Sodium selenate is a specific agonist for PP2A expressing the regulatory B subunit, an essential subunit for tau dephosphorylation by PP2A.
“Sodium selenate is a specific agonist for PP2A expressing the regulatory B subunit, an essential subunit for tau dephosphorylation by PP2A (Jones et al., 2012; Liu et al., 2016), and shows promise as a potential antiepileptic treatment option.”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Jones et al., 2012
Sodium selenate treatment attenuates seizure activity and tau hyperphosphorylation and accumulation following pentylenetetrazol or kainic acid administration and in the temporal lobe epilepsy model of amygdala kindling and the fluid percussion injury model of post-traumatic epilepsy.
“Sodium selenate treatment attenuates seizure activity and tau hyperphosphorylation and accumulation following administration of pentylenetetrazol or kainic acid as well as in the TLE model of amygdala kindling and the fluid percussion injury model of PTE (Jones et al., 2012; Liu et al., 2016).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Jones et al., 2012
Cites
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Dysregulation of tau phosphorylation in mouse brain during excitotoxic damage.
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Substrate-specific reduction of PP2A activity exaggerates tau pathology
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Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · see citing works
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Liu, S.-J., Zheng, P., Wright, D. K., Dezsi, G., Braine, E., Nguyen, T., Corcoran, N. M., Johnston, L. A., Hovens, C. M., Mayo, J. N., et al. (2016) · Brain · doi:10.1093/brain/aww116 · Cited by 127 · see citing works
Self-citationTau-induced pathology in epilepsy and dementia: notions from patients and animal models.
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Interweaving epilepsy and neurodegeneration: Vitamin E as a treatment approach
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Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms
Hwang, K., Vaknalli, R. N., Addo-Osafo, K., Vicente, M., & Vossel, K. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.903973 · Cited by 35 · see citing works
- Authors
- Jones, N. C., Nguyen, T., Corcoran, N. M., Velakoulis, D., Chen, T., Grundy, R., O'Brien, T. J., & Hovens, C. M.
- Affiliations
- The Royal Melbourne Hospital (AU)
- National Institutes of Health (US)
- Corresponding author
- Hovens, Christopher M.
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 45
- Issue
- 3
- Pages
- 897-901
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2084881114
- Cited by
- 81
- References
- 3
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NHMRC (1006077)
- VNI (DNP13)
- Velacor Therapeutics
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- hyperphosphorylated tau, sodium selenate, seizures, epilepsy, protein phosphatase 2A, okadaic acid, amygdala kindling, pentylenetetrazole-induced seizures
- MeSH terms
- Amygdala, Analysis of Variance, Animals, Antioxidants, Convulsants, Disease Models, Animal, Dose-Response Relationship, Drug, Electric Stimulation, Enzyme Inhibitors, Gene Expression Regulation, Humans, Leucine, Male, Mutation, Neuroblastoma, Pentylenetetrazole, Phosphorylation, Proline, Seizures, Time Factors, Transfection, tau Proteins, Rats, Sprague-Dawley, Rats, Wistar, Selenium Compounds, Okadaic Acid, Cell Line, Tumor, Rats, Selenic Acid
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