Non-24-Hour Sleep-Wake Disorder Revisited - A Case Study.

The human sleep-wake cycle is governed by two major factors: a homeostatic hourglass process (process S), which rises linearly during the day, and a circadian process C, which determines the timing of sleep in a ~24-h rhythm in accordance to the external light-dark (LD) cycle. While both individual processes are fairly well characterized, the exact nature of their interaction remains unclear. The circadian rhythm is generated by the suprachiasmatic nucleus ("master clock") of the anterior hypothalamus, through cell-autonomous feedback loops of DNA transcription and translation.

Serum factors in older individuals change cellular clock properties.

Human aging is accompanied by dramatic changes in daily sleep-wake behavior: Activity shifts to an earlier phase, and the consolidation of sleep and wake is disturbed. Although this daily circadian rhythm is brain-controlled, its mechanism is encoded by cell-autonomous circadian clocks functioning in nearly every cell of the body. In fact, human clock properties measured in peripheral cells such as fibroblasts closely mimic those measured physiologically and behaviorally in the same subjects.

The physiological period length of the human circadian clock in vivo is directly proportional to period in human fibroblasts.

Background: Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls"), clock properties measured in human fibroblasts correlated with extreme diurnal behavior.

Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure.

Background: Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta) in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Abeta-induced defects in energy metabolism.

Abeta and human amylin share a common toxicity pathway via mitochondrial dysfunction.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are leading causes of morbidity and mortality in the elderly. Both diseases are characterized by amyloid deposition in target tissues: aggregation of amylin in T2DM is associated with loss of insulin-secreting beta-cells, while amyloid beta (A beta) aggregation in AD brain is associated with neuronal loss. Here, we used quantitative iTRAQ proteomics as a discovery tool to show that both A beta and human amylin (HA) deregulate identical proteins, a quarter of which are mitochondrial, supporting the notion that mitochondrial dysfunction is a common target in these two amyloidoses.

Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice.

Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta)-containing plaques, neurofibrillary tangles, and neuron and synapse loss. Tangle formation has been reproduced in P301L tau transgenic pR5 mice, whereas APP(sw)PS2(N141I) double-transgenic APP152 mice develop Abeta plaques. Cross-breeding generates triple transgenic ((triple)AD) mice that combine both pathologies in one model.

Immunohistochemical Localization of Fas-associated phosphatase-1 (FAP-1) in Alzheimer disease hippocampus.

Fas-associated phosphatase-1 (FAP-1) is a regulatory peptide inhibiting apoptotic signal transduction via the death receptor Fas. Because apoptosis is a common mechanism leading to neuronal death in neurodegenerative disorders, the authors investigated the immunohistochemical distribution of FAP-1 in the hippocampus of elderly control subjects and Alzheimer disease (AD) patients. The current study provides the first evidence that FAP-1 is localized in the human hippocampus in pyramidal neurons of the hippocampal subfields CA1-4 and in granular cells.

Immunohistochemical localization of angiotensin-converting enzyme, angiotensin II and AT1 receptor in human ocular tissues.

We investigated the immunohistochemical distribution of 3 components of the renin-angiotensin system (RAS), angiotensin-converting enzyme (ACE), angiotensin II (AngII) and AT1 receptor (AT1), in the human eye. ACE and AngII were localized to nonpigmented epithelial cells of the ciliary body, to endothelial and epithelial cells of the cornea, to epithelial cells of the conjunctiva and to trabecular meshwork cells in the anterior part of the eye. In the posterior part of the eye, ACE and AngII were localized to ganglion cells, some cells in the inner nuclear layer, photoreceptor cells and to endothelial cells of the retinal and choroidal vessels.

Reduced hippocampal MT2 melatonin receptor expression in Alzheimer's disease.

The aim of the present study was to identify the distribution of the second melatonin receptor (MT2) in the human hippocampus of elderly controls and Alzheimer's disease (AD) patients. This is the first report of immunohistochemical MT2 localization in the human hippocampus both in control and AD cases. The specificity of the MT2 antibody was ascertained by fluorescence microscopy using the anti-MT2 antibody in HEK 293 cells expressing recombinant MT2, in immunoblot experiments on membranes from MT2 expressing cells, and, finally, by immunoprecipitation experiments of the native MT2.

Orexins and their receptors in the human retina.

Objectives: Orexins A and B are neuropeptides involved in the regulation of feeding behavior, energy homeostasis and arousal. In the human retina, however, immunohistochemical localization of orexins and their receptors, OX-R1 and OX-R2, has not been ascertained.

Methods: We localized orexins A and B, OX-R1 and OX-R2 in the human retina using immunohistochemistry.

Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity.

Background: beta-Amyloid peptide (Abeta), a neutrotoxic substance, has been implicated to a great degree in cell death during the course of AD. Resveratrol, a natural polyphenol mainly found in red wine, has been shown to be cardioprotective and chemoprotective. Since a moderate wine intake correlates with a lower risk for Alzheimer disease (AD), an additional neuroprotective effect has been postulated for resveratrol.

Increased melatonin 1a-receptor immunoreactivity in the hippocampus of Alzheimer's disease patients.

The pineal secretory product melatonin has, in addition to regulating retinal, circadian and vascular functions, neuroprotective effects. Blood melatonin levels are often decreased in Alzheimer's disease (AD), a progressively disabling neurodegenerative disorder. In this study we provide the first immunohistochemical evidence for the localization of melatonin 1a-receptor (MT(1)) in aged human hippocampus and a comparison of AD cases.