Circadian Disruption Reveals a Correlation of an Oxidative GSH/GSSG Redox Shift with Learning and Impaired Memory in an Alzheimer's Disease Mouse Model.

It is unclear whether pre-symptomatic Alzheimer's disease (AD) causes circadian disruption or whether circadian disruption accelerates AD pathogenesis. In order to examine the sensitivity of learning and memory to circadian disruption, we altered normal lighting phases by an 8 h shortening of the dark period every 3 days (jet lag) in the APPSwDI NOS2-/- model of AD (AD-Tg) at a young age (4-5 months), when memory is not yet affected compared to non-transgenic (non-Tg) mice. Analysis of activity in 12-12 h lighting or constant darkness showed only minor differences between AD-Tg and non-Tg mice.

Sexual history taking in the emergency department - more specificity required.

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are the most reported diseases in the United States, and emergency departments (ED) serve a population presenting with increased infection risk. However, identifying patients for whom sexually transmitted infection (STI) screening is appropriate requires accurate sexual history reporting.

Study Objectives: To examine the consistency with which ED patients answer general and specific sexual activity questions, and how responses relate to perceived STI risk.

Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons.

Aging, a major risk factor in Alzheimer's disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance.

Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS.

A reversible early oxidized redox state that precedes macromolecular ROS damage in aging nontransgenic and 3xTg-AD mouse neurons.

The brain depends on redox electrons from nicotinamide adenine dinucleotide (reduced form; NADH) to produce ATP and oxyradicals (reactive oxygen species [ROS]). Because ROS damage and mitochondrial dysregulation are prominent in aging and Alzheimer's disease (AD) and their relationship to the redox state is unclear, we wanted to know whether an oxidative redox shift precedes these markers and leads to macromolecular damage in a mouse model of AD. We used the 3xTg-AD mouse model, which displays cognitive deficits beginning at 4 months.