Management of sleep/wake cycles improves cognitive function in a transgenic mouse model of Huntington's disease

Pallier, Patrick N.; Morton, A. Jennifer

doi:10.1016/j.brainres.2009.03.072

Cited by 79 publications

(53 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transgenic mouse models of HD have shown that improving circadian and sleep patterns using Alprazolam can actually improve cognitive function and survival in R6/ 2 mice [116,117]. Another recent study has shown that arrhythmic hamsters fail to perform in a hippocampaldependant learning task and that learning can be restored using a GABA antagonist [143].…”

Section: Possible Causes Of Sleep Disturbance In Hdmentioning

confidence: 95%

How vital is sleep in Huntington’s disease?

Goodman

Barker

2010

J Neurol

View full text Add to dashboard Cite

Huntington's disease (HD) is a fatal neurodegenerative disease caused by an abnormal expansion of a CAG repeat in exon 1 of the HD gene on chromosome 4. The disease runs a debilitating and progressive course with an average survival of 15-25 years after disease onset. HD patients classically develop involuntary movements including chorea, as well as progressive cognitive and psychiatric disturbances, although a number of other features have also been reported, including changes in sleep and circadian rhythms; it is this latter area that forms the focus of this review.

show abstract

Section: Possible Causes Of Sleep Disturbance In Hdmentioning

confidence: 95%

How vital is sleep in Huntington’s disease?

Goodman

Barker

2010

J Neurol

View full text Add to dashboard Cite

show abstract

“…We showed previously that circadian rhythms of rest and activity, as well as circadian gene expression in the central hypothalamic pacemaker of the suprachiasmatic nuclei (SCN), are disrupted in R6/2 mice (Morton et al, 2005), although the intrinsic molecular machinery for generating circadian rhythms in the SCN remains intact (Pallier et al, 2007). Furthermore, in vivo pharmacological regularization of the sleep-wake disturbance can ameliorate both motor and cognitive dysfunction, and restore some features of SCN gene expression (Pallier et al, 2007;Pallier and Morton, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…In SCN-deficient wild-type (WT) mice, temporally restricted daily feeding (RF) can activate a food-entrainable oscillator (FEO) and thereby reimpose daily patterning to rest and activity (for review, see Mistlberger, 2009). We showed previously that pharmacological manipulations could restore daily patterning to the behavior of R6/2 mice (Pallier and Morton, 2009). Here, by subjecting R6/2 mice to RF, we tested whether the FEO could be activated and used to control the rest/activity cycle in the context of HD.…”

Section: Introductionmentioning

confidence: 99%

Disruption of Peripheral Circadian Timekeeping in a Mouse Model of Huntington's Disease and Its Restoration by Temporally Scheduled Feeding

Maywood

Fraenkel²,

McAllister³

et al. 2010

J. Neurosci.

126

106

View full text Add to dashboard Cite

Behavioral circadian rhythms disintegrate progressively in the R6/2 mouse model of Huntington's disease (HD), recapitulating the sleep-wake disturbance seen in HD patients. Here we show that disturbances in circadian pacemaking are not restricted to the brain, but also encompass peripheral metabolic pathways in R6/2 mice. Notably, circadian rhythms of clock-driven genes that are key metabolic outputs in the liver are abolished in vivo. This deficiency is accompanied by arrhythmic expression of the clock genes Cry1 and Dbp, and a phase-advanced Per2 cycle. Compromised circadian metabolic cycles are not, however, a consequence of deficient pacemaking intrinsic to the liver, because when cultured in vitro, R6/2 liver slices exhibit self-sustained circadian bioluminescence rhythms. We therefore propose that compromised metabolic cycles arise from an internal desynchronization secondary to altered feeding patterns and impaired circadian signaling from the central pacemaker of the suprachiasmatic nucleus (SCN). Importantly, the SCN-independent food-entrainable oscillator remains intact in R6/2 mice and, when invoked, can restore daily behavioral cycles and reverse some of the metabolic abnormalities seen in the liver. Disturbances of metabolism have long been thought to be an important feature of HD. Uncoupling liver metabolism from circadian drives will reduce metabolic efficiency and cause imbalances in metabolites known to be deleterious to brain function. Thus, even subtle imbalances in liver function may exacerbate symptoms of HD, where neurological function is already compromised.

show abstract

“…The predictive value of dampened circadian rhythms for future impairments suggests that age-associated circadian dysfunction aggravates cognitive decline introducing the possibility of circadian rhythm reinforcement as a therapeutic component during treatment of age-related memory impairments. In a mouse model of Huntington's disease, pharmacological manipulation of rest/activity cycles or scheduled feeding as reinforcement of circadian rhythms mitigated metabolic, circadian, and cognitive impairments (Pallier et al 2007;Oosterman et al 2009;Pallier and Morton 2009;Maywood et al 2010). Reinforcing or strengthening circadian rhythms may represent potential treatment options to slow progression of neurodegenerative diseases and the accompanying cognitive declines.…”

Section: The Circadian Clock Aging and Neurodegenerative Diseasesmentioning

confidence: 99%

Synchrony and desynchrony in circadian clocks: impacts on learning and memory

Krishnan

Lyons

2015

Learn. Mem.

View full text Add to dashboard Cite

Circadian clocks evolved under conditions of environmental variation, primarily alternating light dark cycles, to enable organisms to anticipate daily environmental events and coordinate metabolic, physiological, and behavioral activities. However, modern lifestyle and advances in technology have increased the percentage of individuals working in phases misaligned with natural circadian activity rhythms. Endogenous circadian oscillators modulate alertness, the acquisition of learning, memory formation, and the recall of memory with examples of circadian modulation of memory observed across phyla from invertebrates to humans. Cognitive performance and memory are significantly diminished when occurring out of phase with natural circadian rhythms. Disruptions in circadian regulation can lead to impairment in the formation of memories and manifestation of other cognitive deficits. This review explores the types of interactions through which the circadian clock modulates cognition, highlights recent progress in identifying mechanistic interactions between the circadian system and the processes involved in memory formation, and outlines methods used to remediate circadian perturbations and reinforce circadian adaptation.Circadian clocks permit organisms to anticipate recurring daily environmental events through the coordination of metabolic, physiological, and behavioral rhythms. Conservation of the core principles through which circadian oscillators are organized across eukaryotic phyla suggests strong selective pressures for both circadian clocks and the mechanisms through which circadian oscillators operate. Intracellularly, transcription/translation feedback loops involving core circadian components set the stage for transcriptional regulation of thousands of genes in individual cells and tissues (Balsalobre et al.

show abstract

Management of sleep/wake cycles improves cognitive function in a transgenic mouse model of Huntington's disease

Cited by 79 publications

References 41 publications

How vital is sleep in Huntington’s disease?

How vital is sleep in Huntington’s disease?

Disruption of Peripheral Circadian Timekeeping in a Mouse Model of Huntington's Disease and Its Restoration by Temporally Scheduled Feeding

Synchrony and desynchrony in circadian clocks: impacts on learning and memory

Contact Info

Product

Resources

About