東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

The Effect of Cicadian Therapies in ...

Whittaker, Daniel Steven.

FindBook

Google Book

Amazon

博客來

The Effect of Cicadian Therapies in Models of Neurodegenerative Disease.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The Effect of Cicadian Therapies in Models of Neurodegenerative Disease./
作者:	Whittaker, Daniel Steven.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	144 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Contained By:	Dissertations Abstracts International81-05B.
標題:	Physiology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22624748
ISBN:	9781687967176

The Effect of Cicadian Therapies in Models of Neurodegenerative Disease.
Whittaker, Daniel Steven.

The Effect of Cicadian Therapies in Models of Neurodegenerative Disease. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 144 p.

Source: Dissertations Abstracts International, Volume: 81-05, Section: B.

Thesis (Ph.D.)--University of California, Los Angeles, 2019.

This item must not be sold to any third party vendors.

Huntington's Disease (HD) is an autosomal dominant disorder caused by excessive CAG repeats in the gene encoding the huntingtin protein which leads to progressive neurodegeneration that inflicts cognitive, psychiatric, cardiovascular and motor dysfunction. There is currently no treatment to prevent or delay the course of the disease. Neuronal loss in the striatum is thought to be responsible for the abnormal motor control present in HD patients, though the pathophysiology behind the non-motor symptoms is still unclear. Disturbances in sleep-wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and excessive fatigue, and these disruptions are recapitulated in mouse models. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early interventions that improve circadian rhythmicity could benefit HD symptoms and delay disease progression. Evidence of altered histaminergic signaling in HD patients suggests that this pathway may contribute to disrupted rhythms in arousal. Utilizing the Q175 mouse model of HD, we demonstrated that nightly treatment with a histamine-3 receptor antagonist/inverse agonist improved several behavioral measures of HD including strengthening activity rhythms, cognitive performance, and mood, as well as reducing inappropriate activity during the normal sleep time. Our findings suggest that drugs targeting the histamine-3 receptor system may be beneficial as cognitive enhancers in the management of HD.One of the most powerful regulators of the circadian system is the daily feed/fast cycle, and in two separate studies we found that three months of time-restricted feeding (6-hours of feeding in the middle of the active phase followed by 18-hours fasting) improved the sleep/wake cycle, motor symptoms, and autonomic function in both the Q175 and BACHD mouse models.Finally, we sought to determine whether a ketogenic diet was sufficient to impart motor performance and sleep/wake rhythm benefits in BACHD mice similar to those observed under TRF. We found that the ketogenic diet improves circadian dysfunction as well as motor symptoms in the BACHD mouse model.Altogether, these studies support the hypothesis that early interventions that improve sleep/wake timing and circadian rhythmicity can ameliorate a range of symptoms of HD and related neurodegenerative disorders.

ISBN: 9781687967176Subjects--Topical Terms:

518431
Physiology.
Subjects--Index Terms:

Circadian rhythms

The Effect of Cicadian Therapies in Models of Neurodegenerative Disease.
LDR:03663nmm a2200385 4500 001 2272821
005 20201105110232.5
008 220629s2019 ||||||||||||||||| ||eng d
020 $a 9781687967176
035 $a (MiAaPQ)AAI22624748
035 $a AAI22624748
040 $a MiAaPQ $c MiAaPQ
100 1 $a Whittaker, Daniel Steven. $3 3550245
245 1 4 $a The Effect of Cicadian Therapies in Models of Neurodegenerative Disease.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 144 p.
500 $a Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
500 $a Advisor: Colwell, Christopher S.
502 $a Thesis (Ph.D.)--University of California, Los Angeles, 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Huntington's Disease (HD) is an autosomal dominant disorder caused by excessive CAG repeats in the gene encoding the huntingtin protein which leads to progressive neurodegeneration that inflicts cognitive, psychiatric, cardiovascular and motor dysfunction. There is currently no treatment to prevent or delay the course of the disease. Neuronal loss in the striatum is thought to be responsible for the abnormal motor control present in HD patients, though the pathophysiology behind the non-motor symptoms is still unclear. Disturbances in sleep-wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and excessive fatigue, and these disruptions are recapitulated in mouse models. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early interventions that improve circadian rhythmicity could benefit HD symptoms and delay disease progression. Evidence of altered histaminergic signaling in HD patients suggests that this pathway may contribute to disrupted rhythms in arousal. Utilizing the Q175 mouse model of HD, we demonstrated that nightly treatment with a histamine-3 receptor antagonist/inverse agonist improved several behavioral measures of HD including strengthening activity rhythms, cognitive performance, and mood, as well as reducing inappropriate activity during the normal sleep time. Our findings suggest that drugs targeting the histamine-3 receptor system may be beneficial as cognitive enhancers in the management of HD.One of the most powerful regulators of the circadian system is the daily feed/fast cycle, and in two separate studies we found that three months of time-restricted feeding (6-hours of feeding in the middle of the active phase followed by 18-hours fasting) improved the sleep/wake cycle, motor symptoms, and autonomic function in both the Q175 and BACHD mouse models.Finally, we sought to determine whether a ketogenic diet was sufficient to impart motor performance and sleep/wake rhythm benefits in BACHD mice similar to those observed under TRF. We found that the ketogenic diet improves circadian dysfunction as well as motor symptoms in the BACHD mouse model.Altogether, these studies support the hypothesis that early interventions that improve sleep/wake timing and circadian rhythmicity can ameliorate a range of symptoms of HD and related neurodegenerative disorders.
590 $a School code: 0031.
650 4 $a Physiology. $3 518431
650 4 $a Molecular biology. $3 517296
650 4 $a Cellular biology. $3 3172791
653 $a Circadian rhythms
653 $a feed/fast cycle
653 $a Huntington's disease
653 $a ketogenic diet
653 $a neurodegeneration
653 $a time-restricted feeding
690 $a 0719
690 $a 0307
690 $a 0379
710 2 $a University of California, Los Angeles. $b Molec, Cell, & Integ Physiology 0568. $3 3181612
773 0 $t Dissertations Abstracts International $g 81-05B.
790 $a 0031
791 $a Ph.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=22624748