Neurophysiological and Behavioral Effects of Anti-Orexinergic Treatments in a Mouse Model of Huntington's Disease

Cabanas, Magali; Pistono, Cristiana; Puygrenier, Laura; Rakesh, Divyangana; Jeantet, Yannick; Garret, Maurice; Cho, Yoon Hi

doi:10.1007/s13311-019-00726-3

Cited by 19 publications

(14 citation statements)

References 67 publications

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“…observed that orexin in HD has aberrant effect leads to abnormal sleep pattern, and thus orexin antagonist suvorexant may be of great value in restoring normal sleep and behavioral disturbance in HD. [ 81 ] in addition, despite reduction of orexinergic density in HD, these neurons remain functional and illustrate paradoxical effect, it become more modifiable and affect by serotonine and noradrenaline, and less sensitive to the effect of suprachiasmatic nucleus (the master clock of the brain) causing abnormal biological circadian rhythm. [ 81 82 ]…”

Section: Role Of Orexin In Neurodegenerative Diseasesmentioning

confidence: 99%

Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review

et al. 2020

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Orexin is a neuropeptide secreted from lateral hypothalamus and pre-frontal cortex concerned in the wakefulness and excitement. This study aimed to review the possible neurobiological effect of orexin. A diversity of search strategies was adopted and assumed which included electronic database searches of Medline and PubMed using MeSH terms, keywords, and title words during the search. Orexin plays a vital role in activation of learning, memory acquisition, and consolidation through activation of monoaminergic system, which affect cognitive flexibility and cognitive function. Orexin stimulates adrenocorticotropin and corticosteroid secretions via activation of central corticotropin-releasing hormone. Cerebrospinal fluid (CSF) and serum orexin serum levels are reduced in depression, schizophrenia, and narcolepsy. However, high orexin serum levels are revealed in drug addictions. Regarding neurodegenerative brain diseases, CSF and serum orexin serum levels are reduced Parkinson disease, Alzheimer dementia, Huntington's disease, amyotrphic lateral sclerosis, and multiple sclerosis. Orexin antagonist leads to significant reduction of sympathetic over-activity during withdrawal syndrome. As well, orexin antagonist improves sleep pattern. Orexinergic system is involved in the different psychiatric and neurological disorders; therefore, targeting of this system could be possible novel pathway in the management of these disorders. In addition, measurement of CSF and serum orexin levels might predict the relapse and withdrawal of addict patients.

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Section: Role Of Orexin In Neurodegenerative Diseasesmentioning

confidence: 99%

Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review

et al. 2020

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“…Nonetheless, a further study of light-mediated circadian entrainment in transgenic HD mice has demonstrated improved survival rates [ 92 ], and another employing timed feeding as a circadian cue has also reported improved motor outcomes [ 93 ]. The most recent pre-clinical study of sleep therapy in HD, using an orexin antagonist, has also demonstrated benefit to cognitive outcome [ 94 ].…”

Section: Sleep and Circadian Abnormalities In Huntington’s Disease: Evidence To Datementioning

confidence: 99%

The sleep and circadian problems of Huntington’s disease: when, why and their importance

2020

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Introduction Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases. Findings This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. It is this that makes understanding sleep and circadian abnormalities in Huntington’s disease (HD) important: as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapies at a preclinical or early disease stage. Moreover, its monogenic nature facilitates the development of transgenic animal models through which to run parallel pre-clinical studies. HD, therefore, provides a key model condition through which to gain new insights into the sleep-neurodegeneration interface. Conclusions Here, we begin by summarising contemporary knowledge of sleep abnormalities in HD, and consider how well these parallel those of Alzheimer’s and Parkinson’s as more common neurodegenerative conditions. We then discuss what is currently known of the sleep-neurodegeneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.

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“…These changes are also consistently observed in animal models of disease, and are attributed to degeneration of the suprachiasmatic nucleus, hypothalamus and striatum. 60,61 They can also occur early in the condition and are associated with higher levels of cognitive impairment and anxiety. 62 Human post-mortem studies have shown a loss of orexin-releasing neurons in individuals diagnosed with HD, while transgenic HD mouse models suggest that changes to SCN circuitry are central in driving circadian disruption.…”

Section: Sleep Disorders In Huntington's Disease (Hd)mentioning

confidence: 99%

“…62 Human post-mortem studies have shown a loss of orexin-releasing neurons in individuals diagnosed with HD, while transgenic HD mouse models suggest that changes to SCN circuitry are central in driving circadian disruption. 60…”

Section: Sleep Disorders In Huntington's Disease (Hd)mentioning

confidence: 99%

Sleep disturbance in movement disorders: insights, treatments and challenges

Bailey

Hubbard

Fasano

et al. 2021

J Neurol Neurosurg Psychiatry

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Sleep and circadian rhythm disturbances are central features of many movement disorders, exacerbating motor and non-motor symptoms and impairing quality of life. Understanding these disturbances to sleep is clinically important and may further our understanding of the underlying movement disorder. This review evaluates the current anatomical and neurochemical understanding of normal sleep and the recognised primary sleep disorders. In addition, we undertook a systematic review of the evidence for disruption to sleep across multiple movement disorders. Rapid eye movement sleep behaviour disorder has emerged as the most reliable prodromal biomarker for the alpha synucleinopathies, including Parkinson’s disease and multiple system atrophy, often preceding motor symptom onset by several years. Abnormal sleep has also been described for many other movement disorders, but further evidence is needed to determine whether this is a primary or secondary phenotypic component of the underlying condition. Medication used in the treatment of motor symptoms also affects sleep and can aggravate or cause certain sleep disorders. Within the context of movement disorders, there is also some suggestion of a shared underlying mechanism for motor and sleep pathophysiology, with evidence implicating thalamic and brainstem structures and monoaminergic neurotransmission. This review highlights the need for an understanding of normal and abnormal sleep within the movement disorder clinic, an ability to screen for specific causes of poor sleep and to treat sleep disturbance to improve quality of life. Key sleep disorders also act as important biomarkers and have implications in diagnosis, prognosis and the development of future therapies.

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Neurophysiological and Behavioral Effects of Anti-Orexinergic Treatments in a Mouse Model of Huntington's Disease

Cited by 19 publications

References 67 publications

Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review

Involvement of orexinergic system in psychiatric and neurodegenerative disorders: A scoping review

The sleep and circadian problems of Huntington’s disease: when, why and their importance

Sleep disturbance in movement disorders: insights, treatments and challenges

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