Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy
A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer’s disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better w...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2020.570223/full |
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| author | Tariq Ahmed Tariq Ahmed Ann Van der Jeugd Ann Van der Jeugd Raphaëlle Caillierez Raphaëlle Caillierez Luc Buée Luc Buée David Blum David Blum Rudi D’Hooge Rudi D’Hooge Detlef Balschun Detlef Balschun |
| author_facet | Tariq Ahmed Tariq Ahmed Ann Van der Jeugd Ann Van der Jeugd Raphaëlle Caillierez Raphaëlle Caillierez Luc Buée Luc Buée David Blum David Blum Rudi D’Hooge Rudi D’Hooge Detlef Balschun Detlef Balschun |
| author_sort | Tariq Ahmed |
| collection | DOAJ |
| description | A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer’s disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyloid-β load, supporting a key role of tau-related mechanisms. Selenium is a non-metallic trace element that is incorporated in the brain into selenoproteins. Chronic treatment with sodium selenate, a non-toxic selenium compound, was recently reported to rescue behavioral phenotypes in tau mouse models. Here, we focused on the effects of chronic selenate application on synaptic transmission and synaptic plasticity in THY-Tau22 mice, a transgenic animal model of tauopathies. Three months with a supplement of sodium selenate in the drinking water (12 μg/ml) restored not only impaired neurocognitive functions but also rescued long-term depression (LTD), a major form of synaptic plasticity. Furthermore, selenate reduced the inactive demethylated catalytic subunit of protein phosphatase 2A (PP2A) in THY-Tau22 without affecting total PP2A.Our study provides evidence that chronic dietary selenate rescues functional synaptic deficits of tauopathy and identifies activation of PP2A as the putative mechanism. |
| first_indexed | 2024-12-23T11:04:02Z |
| format | Article |
| id | doaj.art-92bf986f882a49b0ac67f35e58e84c5e |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-23T11:04:02Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-92bf986f882a49b0ac67f35e58e84c5e2022-12-21T17:49:32ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992020-10-011310.3389/fnmol.2020.570223570223Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of TauopathyTariq Ahmed0Tariq Ahmed1Ann Van der Jeugd2Ann Van der Jeugd3Raphaëlle Caillierez4Raphaëlle Caillierez5Luc Buée6Luc Buée7David Blum8David Blum9Rudi D’Hooge10Rudi D’Hooge11Detlef Balschun12Detlef Balschun13Brain and Cognition, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, BelgiumLeuven Brain Institute, Leuven, BelgiumLeuven Brain Institute, Leuven, BelgiumLaboratory of Biological Psychology, Brain and Cognition, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, BelgiumUniv. Lille, Inserm, CHU Lille, U1172—LilNCog—Lille Neuroscience and Cognition, Lille, FranceAlzheimer and Tauopathies, LabEx DISTALZ, Lille, FranceUniv. Lille, Inserm, CHU Lille, U1172—LilNCog—Lille Neuroscience and Cognition, Lille, FranceAlzheimer and Tauopathies, LabEx DISTALZ, Lille, FranceUniv. Lille, Inserm, CHU Lille, U1172—LilNCog—Lille Neuroscience and Cognition, Lille, FranceAlzheimer and Tauopathies, LabEx DISTALZ, Lille, FranceLeuven Brain Institute, Leuven, BelgiumLaboratory of Biological Psychology, Brain and Cognition, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, BelgiumBrain and Cognition, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, BelgiumLeuven Brain Institute, Leuven, BelgiumA major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer’s disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyloid-β load, supporting a key role of tau-related mechanisms. Selenium is a non-metallic trace element that is incorporated in the brain into selenoproteins. Chronic treatment with sodium selenate, a non-toxic selenium compound, was recently reported to rescue behavioral phenotypes in tau mouse models. Here, we focused on the effects of chronic selenate application on synaptic transmission and synaptic plasticity in THY-Tau22 mice, a transgenic animal model of tauopathies. Three months with a supplement of sodium selenate in the drinking water (12 μg/ml) restored not only impaired neurocognitive functions but also rescued long-term depression (LTD), a major form of synaptic plasticity. Furthermore, selenate reduced the inactive demethylated catalytic subunit of protein phosphatase 2A (PP2A) in THY-Tau22 without affecting total PP2A.Our study provides evidence that chronic dietary selenate rescues functional synaptic deficits of tauopathy and identifies activation of PP2A as the putative mechanism.https://www.frontiersin.org/article/10.3389/fnmol.2020.570223/fullAlzheimer’s diseasechronic oral treatmentsynaptic transmissionsynaptic plasticitylong-term depressionneurocognitive functions |
| spellingShingle | Tariq Ahmed Tariq Ahmed Ann Van der Jeugd Ann Van der Jeugd Raphaëlle Caillierez Raphaëlle Caillierez Luc Buée Luc Buée David Blum David Blum Rudi D’Hooge Rudi D’Hooge Detlef Balschun Detlef Balschun Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy Frontiers in Molecular Neuroscience Alzheimer’s disease chronic oral treatment synaptic transmission synaptic plasticity long-term depression neurocognitive functions |
| title | Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy |
| title_full | Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy |
| title_fullStr | Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy |
| title_full_unstemmed | Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy |
| title_short | Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy |
| title_sort | chronic sodium selenate treatment restores deficits in cognition and synaptic plasticity in a murine model of tauopathy |
| topic | Alzheimer’s disease chronic oral treatment synaptic transmission synaptic plasticity long-term depression neurocognitive functions |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2020.570223/full |
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