Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model
Angelman syndrome (AS) is a rare genetic and neurological disorder presenting with seizures, developmental delay, ataxia, and lack of speech. Previous studies have indicated that oxidative stress-dependent metabolic dysfunction may underlie the phenotypic deficits reported in the AS mouse model. Whi...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999611630198X |
| _version_ | 1818742131930431488 |
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| author | Stephanie L. Ciarlone Joseph C. Grieco Dominic P. D'Agostino Edwin J. Weeber |
| author_facet | Stephanie L. Ciarlone Joseph C. Grieco Dominic P. D'Agostino Edwin J. Weeber |
| author_sort | Stephanie L. Ciarlone |
| collection | DOAJ |
| description | Angelman syndrome (AS) is a rare genetic and neurological disorder presenting with seizures, developmental delay, ataxia, and lack of speech. Previous studies have indicated that oxidative stress-dependent metabolic dysfunction may underlie the phenotypic deficits reported in the AS mouse model. While the ketogenic diet (KD) has been used to protect against oxidative stress and has successfully treated refractory epilepsy in AS case studies, issues arise due to its strict adherence requirements, in addition to selective eating habits and weight issues reported in patients with AS. We hypothesized that ketone ester supplementation would mimic the KD as an anticonvulsant and improve the behavioral and synaptic plasticity deficits in vivo. AS mice were supplemented R,S-1,3-butanediol acetoacetate diester (KE) ad libitum for eight weeks. KE administration improved motor coordination, learning and memory, and synaptic plasticity in AS mice. The KE was also anticonvulsant and altered brain amino acid metabolism in AS treated animals. Our findings suggest that KE supplementation produces sustained ketosis and ameliorates many phenotypes in the AS mouse model, and should be investigated further for future clinical use. |
| first_indexed | 2024-12-18T02:07:39Z |
| format | Article |
| id | doaj.art-0c47e62a9c154abf8c06e0b380b4b76c |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-18T02:07:39Z |
| publishDate | 2016-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-0c47e62a9c154abf8c06e0b380b4b76c2022-12-21T21:24:33ZengElsevierNeurobiology of Disease1095-953X2016-12-01963846Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse modelStephanie L. Ciarlone0Joseph C. Grieco1Dominic P. D'Agostino2Edwin J. Weeber3USF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, United StatesUSF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, United StatesDepartment of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, United StatesUSF Health Byrd Alzheimer's Institute, Tampa, FL 33613, United States; Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, FL 33620, United States; Corresponding author at: Byrd Alzheimer's Institute, 4001 East Fletcher Avenue, Tampa, FL 33613, United States.Angelman syndrome (AS) is a rare genetic and neurological disorder presenting with seizures, developmental delay, ataxia, and lack of speech. Previous studies have indicated that oxidative stress-dependent metabolic dysfunction may underlie the phenotypic deficits reported in the AS mouse model. While the ketogenic diet (KD) has been used to protect against oxidative stress and has successfully treated refractory epilepsy in AS case studies, issues arise due to its strict adherence requirements, in addition to selective eating habits and weight issues reported in patients with AS. We hypothesized that ketone ester supplementation would mimic the KD as an anticonvulsant and improve the behavioral and synaptic plasticity deficits in vivo. AS mice were supplemented R,S-1,3-butanediol acetoacetate diester (KE) ad libitum for eight weeks. KE administration improved motor coordination, learning and memory, and synaptic plasticity in AS mice. The KE was also anticonvulsant and altered brain amino acid metabolism in AS treated animals. Our findings suggest that KE supplementation produces sustained ketosis and ameliorates many phenotypes in the AS mouse model, and should be investigated further for future clinical use.http://www.sciencedirect.com/science/article/pii/S096999611630198XAngelman syndromeSeizureKetone esterMotor coordinationMetabolismSynaptic plasticity |
| spellingShingle | Stephanie L. Ciarlone Joseph C. Grieco Dominic P. D'Agostino Edwin J. Weeber Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model Neurobiology of Disease Angelman syndrome Seizure Ketone ester Motor coordination Metabolism Synaptic plasticity |
| title | Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model |
| title_full | Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model |
| title_fullStr | Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model |
| title_full_unstemmed | Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model |
| title_short | Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model |
| title_sort | ketone ester supplementation attenuates seizure activity and improves behavior and hippocampal synaptic plasticity in an angelman syndrome mouse model |
| topic | Angelman syndrome Seizure Ketone ester Motor coordination Metabolism Synaptic plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S096999611630198X |
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