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Efficacy of Diet Therapies in the Treatm... - Document (1 M) |
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| Author |
Mantis, John G. |
| Title |
Efficacy of Diet Therapies in the Treatment of Neurological and Neurodegenerative Diseases |
| Date created |
2010 |
| Abstract |
Epilepsy is a prevalent disabling chronic and socially isolating neurological disorder that involves recurrent abnormal discharges of neurons. Despite seizures afflicting about 10% of people worldwide, antiepileptic drugs (AEDs) are largely unable to manage seizures in many persons with epilepsy. As an alternative to AEDs, dietary therapies possess a broad therapeutic potential in both humans and animals models of various neurological and neurodegenerative disease etiologies. My research focus was to identify the therapeutic efficacy and potential mechanism(s) of action of calorie restriction (CR) and the ketogenic diet (KD) in both the epileptic EL mouse model and the Mecp2<super>308/y<super/> mouse model of Rett syndrome. My findings indicate that both the KD and CR can reduce seizure susceptibility in EL mice, a natural model for multifactorial idiopathic generalized epilepsy. CR and circulating glucose and ketone levels significantly influence the therapeutic efficacy of the KD. A concurrent reduction in circulating plasma glucose levels and elevation in circulating plasma &beta-hydroxybutyrate levels was predicted to associate with the anticonvulsant effect of these diets in EL mice. For the first time, I was able to show that a KD fed in unrestricted amount is able to reduce seizure threshold in EL mice. Interestingly, supplementation of calories in the form of carbohydrate in the water of calorie-restricted EL mice results in a diminished anticonvulsant efficacy of the KD. In my effort to elucidate the neuroprotective mechanism(s) associated with these changes in metabolite availability, I started investigating the complex alterations occurring in multiple integrated neural and metabolic processes. Furthermore, I showed that a restricted KD diet improves aspects of the behavioral abnormalities seen in Rett mice, in particular with respect to anxiety. Finally, for the first time, I provide a standardized protocol for the implementation of diet therapies in the management of an array of neurological and neurodegenerative diseases, which ultimately may help elucidate the complex neuroprotective mechanism(s) of CR and the KD. This research overall has provided a new understanding in the therapeutic efficacy of diets in epilepsy and Rett Syndrome. |
| Use Restrictions |
I hereby allow Boston College to include and preserve my dissertation/thesis in electronic form in the Boston College Institutional Repository, which shall include the right to publicly post my dissertation/thesis on the World Wide Web. I will retain copyright ownership, but I grant to Boston College the non-exclusive right to copy, distribute, and publicly display my dissertation/thesis in any form as may be necessary or convenient in the future as file formats, storage media, and distribution mechanisms evolve. |
| Subject |
Calorie Restriction |
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Diet therapies |
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Epileptic EL mouse |
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Glucose and Ketones |
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Ketogenic Diet |
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Rett Syndrome |
| Publisher |
Boston College |
| Link to Item |
2345/1330 |
| Thesis Advisor |
Seyfried, Thomas N. |
| Degree Name |
PhD |
| Degree Grantor |
Boston College. Graduate School of Arts & Sciences. |
| Sys. No. |
000002784 |
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