Melatonin reduces hippocampal β-amyloid generation in rats exposed to chronic intermittent hypoxia

Ng, Kwong‐Man; Lau, Chi-Fai; Fung, Man-Lung

doi:10.1016/j.brainres.2010.07.044

Cited by 37 publications

(21 citation statements)

References 44 publications

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“…Our finding contrasts with two rodent studies using chronic intermittent hypoxia, a model of OSA, which showed increased release of Aβ by neurons and increased intracellular Aβ. 15–16 Based on similar Aβ42:40 ratios between groups and decreased Tau and pTau181 levels in the OSA group, it is unlikely that decreased Aβ40 and Aβ42 levels in the OSA group are due to sink effects of existing amyloid plaques in the OSA group. We propose potential mechanisms that may explain our unexpected finding.…”

Section: Discussionmentioning

confidence: 96%

“…In a pig model, there was decreased Aβ42 in CSF following hypoxia. 21 However, in several different models, hypoxia is associated with increased Aβ, 15–16 through increased expression of β-site amyloid precursor protein cleaving enzyme, 22 decreased degradation by neprilysin, 23 increased intracellular transport of APP, 24 and potentially other mechanisms. Therefore hypoxia associated with OSA is predicted to increase ISF Aβ, even in the setting of decreased neuronal activity.…”

Section: Discussionmentioning

confidence: 99%

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Obstructive sleep apnea decreases central nervous system–derived proteins in the cerebrospinal fluid

Finn²,

Sutphen³

et al. 2016

Annals of Neurology

131

118

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We hypothesized that one mechanism underlying the association between obstructive sleep apnea (OSA) and Alzheimer Disease is OSA leading to decreased slow wave activity, increased synaptic activity, decreased glymphatic clearance, and increased amyloid-β. Polysomnography and lumbar puncture were performed in OSA and control groups. Slow wave activity negatively correlated with cerebrospinal fluid amyloid-β-40 among controls and was decreased in the OSA group. Unexpectedly, amyloid-β-40 was decreased in the OSA group. Other neuronally-derived proteins, but not total protein, were also decreased in the OSA group, suggesting that OSA may affect the interaction between interstitial and cerebrospinal fluid.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Obstructive sleep apnea decreases central nervous system–derived proteins in the cerebrospinal fluid

Finn²,

Sutphen³

et al. 2016

Annals of Neurology

131

118

View full text Add to dashboard Cite

show abstract

“…The role of hypoxia in potentiating AD is supported by the observation that patients suffering from cardiorespiratory disorders, cerebral ischemia or stroke are much more susceptible to development of dementias including AD [31]. It is remarkable that the daily administration of melatonin reduces the hypoxia induced A β generation in the rat hippocampus [32]. …”

Section: Introductionmentioning

confidence: 99%

Melatonin and Its Agonist Ramelteon in Alzheimer′s Disease: Possible Therapeutic Value

Srinivasan

Kaur

Pandi-Perumal³

et al. 2010

International Journal of Alzheimer's Disease

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Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by the progressive loss of cognitive function, loss of memory and insomnia, and abnormal behavioral signs and symptoms. Among the various theories that have been put forth to explain the pathophysiology of AD, the oxidative stress induced by amyloid β-protein (Aβ) deposition has received great attention. Studies undertaken on postmortem brain samples of AD patients have consistently shown extensive lipid, protein, and DNA oxidation. Presence of abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation all have been demonstrated in neural tissues of AD patients. Moreover, AD patients exhibit severe sleep/wake disturbances and insomnia and these are associated with more rapid cognitive decline and memory impairment. On this basis, the successful management of AD patients requires an ideal drug that besides antagonizing Aβ-induced neurotoxicity could also correct the disturbed sleep-wake rhythm and improve sleep quality. Melatonin is an effective chronobiotic agent and has significant neuroprotective properties preventing Aβ-induced neurotoxic effects in a number of animal experimental models. Since melatonin levels in AD patients are greatly reduced, melatonin replacement has the potential value to be used as a therapeutic agent for treating AD, particularly at the early phases of the disease and especially in those in whom the relevant melatonin receptors are intact. As sleep deprivation has been shown to produce oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, and altered proteosomal processing with abnormal activation of enzymes, treatment of sleep disturbances may be a priority for arresting the progression of AD. In this context the newly introduced melatonin agonist ramelteon can be of much therapeutic value because of its highly selective action on melatonin MT1/MT2 receptors in promoting sleep.

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“…Hippocampal A␤ can be reduced by melatonin in rats through BACE-but not presenilin-dependent mechanisms (Ng et al, 2010). In triple transgenic AD mice with 4 weeks of manipulation of oxygenation (5% O 2 and 21% O 2 every 10 min for 8 h/day), there is higher brain A␤42 but not A␤40, and greater intracellular A␤, despite a lack of change of cognitive function.…”

Section: Sleep Disruption and Intermittent Hypoxia Alter A␤ Processinmentioning

confidence: 99%

Can sleep apnea cause Alzheimer's disease?

Pan

Kastin

2014

Neuroscience & Biobehavioral Reviews

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Melatonin reduces hippocampal β-amyloid generation in rats exposed to chronic intermittent hypoxia

Cited by 37 publications

References 44 publications

Obstructive sleep apnea decreases central nervous system–derived proteins in the cerebrospinal fluid

Obstructive sleep apnea decreases central nervous system–derived proteins in the cerebrospinal fluid

Melatonin and Its Agonist Ramelteon in Alzheimer′s Disease: Possible Therapeutic Value

Can sleep apnea cause Alzheimer's disease?

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