Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease
Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington’s disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would amel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2022.1034743/full |
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| author | Daniel S. Whittaker T. Katherine Tamai Raj S. Bains Raj S. Bains Sophia Anne Marie Villanueva Shu Hon Christopher Luk Shu Hon Christopher Luk Derek Dell’Angelica Gene D. Block Cristina A. Ghiani Cristina A. Ghiani Christopher S. Colwell |
| author_facet | Daniel S. Whittaker T. Katherine Tamai Raj S. Bains Raj S. Bains Sophia Anne Marie Villanueva Shu Hon Christopher Luk Shu Hon Christopher Luk Derek Dell’Angelica Gene D. Block Cristina A. Ghiani Cristina A. Ghiani Christopher S. Colwell |
| author_sort | Daniel S. Whittaker |
| collection | DOAJ |
| description | Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington’s disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would ameliorate the symptoms and delay disease progression in the BACHD mouse model of HD. Adult WT and BACHD male mice were fed a normal or a ketogenic diet (KD) for 3 months. The KD evoked a robust rhythm in serum levels of β-hydroxybutyrate and dramatic changes in the microbiome of male WT and BACHD mice. NanoString analysis revealed transcriptional changes driven by the KD in the striatum of both WT and BACHD mice. Disturbances in sleep/wake cycles have been reported in mouse models of HD and are common among HD patients. Having established that the KD had effects on both the WT and mutant mice, we examined its impact on sleep/wake cycles. KD increased daytime sleep and improved the timing of sleep onset, while other sleep parameters were not altered. In addition, KD improved activity rhythms, including rhythmic power, and reduced inappropriate daytime activity and onset variability. Importantly, KD improved motor performance on the rotarod and challenging beam tests. It is worth emphasizing that HD is a genetically caused disease with no known cure. Life-style changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of diet-based treatment strategies in a pre-clinical model of HD. |
| first_indexed | 2024-04-12T14:11:16Z |
| format | Article |
| id | doaj.art-ae7f3030be4548399a07fc4fb7689600 |
| institution | Directory Open Access Journal |
| issn | 2296-861X |
| language | English |
| last_indexed | 2024-04-12T14:11:16Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Nutrition |
| spelling | doaj.art-ae7f3030be4548399a07fc4fb76896002022-12-22T03:29:52ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-11-01910.3389/fnut.2022.10347431034743Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s diseaseDaniel S. Whittaker0T. Katherine Tamai1Raj S. Bains2Raj S. Bains3Sophia Anne Marie Villanueva4Shu Hon Christopher Luk5Shu Hon Christopher Luk6Derek Dell’Angelica7Gene D. Block8Cristina A. Ghiani9Cristina A. Ghiani10Christopher S. Colwell11Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United StatesDisturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington’s disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would ameliorate the symptoms and delay disease progression in the BACHD mouse model of HD. Adult WT and BACHD male mice were fed a normal or a ketogenic diet (KD) for 3 months. The KD evoked a robust rhythm in serum levels of β-hydroxybutyrate and dramatic changes in the microbiome of male WT and BACHD mice. NanoString analysis revealed transcriptional changes driven by the KD in the striatum of both WT and BACHD mice. Disturbances in sleep/wake cycles have been reported in mouse models of HD and are common among HD patients. Having established that the KD had effects on both the WT and mutant mice, we examined its impact on sleep/wake cycles. KD increased daytime sleep and improved the timing of sleep onset, while other sleep parameters were not altered. In addition, KD improved activity rhythms, including rhythmic power, and reduced inappropriate daytime activity and onset variability. Importantly, KD improved motor performance on the rotarod and challenging beam tests. It is worth emphasizing that HD is a genetically caused disease with no known cure. Life-style changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of diet-based treatment strategies in a pre-clinical model of HD.https://www.frontiersin.org/articles/10.3389/fnut.2022.1034743/fullBACHD micecircadian rhythmsketogenic diet (KD)sleepmotor performanceactivity rhythm |
| spellingShingle | Daniel S. Whittaker T. Katherine Tamai Raj S. Bains Raj S. Bains Sophia Anne Marie Villanueva Shu Hon Christopher Luk Shu Hon Christopher Luk Derek Dell’Angelica Gene D. Block Cristina A. Ghiani Cristina A. Ghiani Christopher S. Colwell Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease Frontiers in Nutrition BACHD mice circadian rhythms ketogenic diet (KD) sleep motor performance activity rhythm |
| title | Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease |
| title_full | Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease |
| title_fullStr | Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease |
| title_full_unstemmed | Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease |
| title_short | Dietary ketosis improves circadian dysfunction as well as motor symptoms in the BACHD mouse model of Huntington’s disease |
| title_sort | dietary ketosis improves circadian dysfunction as well as motor symptoms in the bachd mouse model of huntington s disease |
| topic | BACHD mice circadian rhythms ketogenic diet (KD) sleep motor performance activity rhythm |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2022.1034743/full |
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