Transfusion with Blood Plasma from Young Mice Affects rTg4510 Transgenic Tau Mice Modeling of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the buildup of plaques and tangles in the brain. Tangles are formed when the stabilizing protein, tau, becomes hyperphosphorylated and clumps together. There are limited treatments for AD; therefore, the exploration of new treatments is warranted.

White Button Mushroom ( Supplementation Ameliorates Spatial Memory Deficits and Plaque Formation in an Amyloid Precursor Protein Mouse Model of Alzheimer's Disease.

Alzheimer’s Disease (AD) is characterized by cognitive impairment and the presence of amyloid-β (Aβ) plaques and tau tangles. This study was conducted to assess the effects of white button mushroom (WBM) supplementation on spatial memory and plaque formation in mice with mutations in amyloid (Aβ). Mice with amyloid precursor protein (hAPP) mutations and their wildtype (WT) littermates were fed a 10% white button mushroom (WBM) feed ad libitum three times per week, in addition to their normal diet.

Wheel-Running Behavior Is Negatively Impacted by Zinc Administration in a Novel Dual Transgenic Mouse Model of AD.

Alzheimer's disease (AD) is a neurocognitive disorder that impacts both the brain and behavior. Metal ions, including zinc (Zn), have been seen to play an important role in AD-related pathology. In this study, we show alterations in wheel-running behavior both early and late in disease progression in a novel dual Tg mouse model of AD.

Nest Building Behavior as an Early Indicator of Behavioral Deficits in Mice.

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare.

Localization of Free and Bound Metal Species through X-Ray Synchrotron Fluorescence Microscopy in the Rodent Brain and Their Relation to Behavior.

Biometals in the brain, such as zinc, copper, and iron, are often discussed in cases of neurological disorders; however, these metals also have important regulatory functions and mediate cell signaling and plasticity. With the use of synchrotron X-ray fluorescence, our lab localized total, both bound and free, levels of zinc, copper, and iron in a cross section of one hemisphere of a rat brain, which also showed differing metal distributions in different regions within the hippocampus, the site in the brain known to be crucial for certain types of memory. This review discusses the several roles of these metals in brain regions with an emphasis on hippocampal cell signaling, based on spatial mapping obtained from X-ray fluorescence microscopy.

A Novel hAPP/htau Mouse Model of Alzheimer's Disease: Inclusion of APP With Tau Exacerbates Behavioral Deficits and Zinc Administration Heightens Tangle Pathology.

The brains of those with Alzheimer's disease have amyloid and tau pathology; thus, mice modeling AD should have both markers. In this study, we characterize offspring from the cross of the J20 (hAPP) and rTg4510 (htau) strains (referred to as dual Tg). Behavior was assessed at both 3.

Zinc Exacerbates Tau Pathology in a Tau Mouse Model.

Hyperphosphorylated tau protein is a key pathology in Alzheimer's disease (AD), frontotemporal dementia, chronic traumatic encephalopathy, and Parkinson's disease. The essential trace element zinc exacerbates tauopathy in vitro as well as in a Drosophila model of AD. However, the interaction has never been assessed behaviorally or biochemically in mammals.

The Effect of Gentle Handling on Depressive-Like Behavior in Adult Male Mice: Considerations for Human and Rodent Interactions in the Laboratory.

Environmental factors play a significant role in well-being of laboratory animals. Regulations and guidelines recommend, if not require, that stressors such as bright lighting, smells, and noises are eliminated or reduced to maximize animal well-being. A factor that is often overlooked is handling and how researchers interact with their animals.

Localization of the zinc binding tubulin polymerization promoting protein in the mice and human eye.

Tubulin Polymerization Promoting Protein (TPPP/p25) modulates the dynamics and stability of the microtubule network by its bundling and acetylation enhancing activities that can be modulated by the binding of zinc to TPPP/p25. Its expression is essential for the differentiation of oligodendrocytes, the major constituents of the myelin sheath, and has been associated with neuronal inclusions. In this paper, evidence is provided for the expression and localization of TPPP/p25 in the zinc-rich retina and in the oligodendrocytes in the optic nerve.

Circadian wheel running behavior is altered in an APP/E4 mouse model of late onset Alzheimer's disease.

Circadian rhythms are altered in several diseases associated with aging, one of which is Alzheimer's disease (AD). One example of a circadian rhythm is the rest-activity cycle, which can be measured in mice by monitoring their wheel-running. The present study sought to investigate differences in light phase/dark phase activity between a mouse model of late onset AD (APP/E4) and control (C57Bl6J) mice, in both the pre-plaque and post-plaques stages of the disease.

Both Genetic and Environmental Changes Can Enhance Learning and Memory.

This review discusses two papers from the same lab that directly compared the effects of genetic enhancement with environmental enrichment on learning and memory in mice. In the first study mice were genetically manipulated to have an increased expression of the NR2B component of the NMDA receptor, associated with learning. These transgenic (Tg) mice showed greater current flow, larger EPSPs, and improved learning and memory on a variety of tasks.

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye.

Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.

Spatial memory deficits in a mouse model of late-onset Alzheimer's disease are caused by zinc supplementation and correlate with amyloid-beta levels.

Much of the research in Alzheimer's disease (AD) that uses mouse models focuses on the early-onset form of the disease, which accounts for less than 5% of cases. In contrast, this study used a late-onset AD model to examine the interaction between increased dietary zinc (Zn) and the apolipoprotein E (ApoE) gene. ApoE ε4 is overrepresented in late-onset AD and enhances Zn binding to amyloid-β (Aβ).

Human ApoE ε4 alters circadian rhythm activity, IL-1β, and GFAP in CRND8 mice.

Disruptions to daily living, inflammation, and astrogliosis are characteristics of Alzheimer's disease. Thus, circadian rhythms, nest construction, IL-1β and TNF-α, and glial fibrillary acidic protein (GFAP) were examined in a mouse model developed to model late-onset Alzheimer's disease-the most common form of the disease. Mice carrying both the mutated human AβPP transgene found in the CRND8 mouse and the human apolipoprotein E ε4 allele (CRND8/E4) were compared with CRND8 mice and wildtype (WT) mice.

Correlations in distribution and concentration of calcium, copper and iron with zinc in isolated extracellular deposits associated with age-related macular degeneration.

Zinc (Zn) is abundantly enriched in sub-retinal pigment epithelial (RPE) deposits, the hallmarks of age-related macular degeneration (AMD), and is thought to play a role in the formation of these deposits. However, it is not known whether Zn is the only metal relevant for sub-RPE deposit formation. Because of their involvement in the pathogenesis of AMD, we determined the concentration and distribution of calcium (Ca), iron (Fe) and copper (Cu) and compared these with Zn in isolated and sectioned macular (MSD), equatorial (PHD) and far peripheral (FPD) sub-RPE deposits from an 86 year old donor eye with post mortem diagnosis of early AMD.

Indications of reduced prefrontal cortical function in chronically homeless adults.

This study investigated why some homeless individuals seem unable to transition towards self-reliance, following traditional supportive services. It was hypothesized that this may be due to some cognitive dysfunction. Chronically homeless adults were compared to controls on three tests of prefrontal competency: the Iowa Gambling Task, Word Fluency (FAS), and the Burglar's Story; they performed significantly worse than controls on all three tests.

The effect of metals on spatial memory in a transgenic mouse model of Alzheimer's disease.

The amyloid-β protein (Aβ) is a metalloprotein with affinity for the metal ions zinc (Zn), copper (Cu), and iron (Fe), which are found in high concentrations in the plaques of Alzheimer's disease (AD). Increasing attention is focused on the role of these metals in AD, and much of the evidence suggests a dyshomeostasis between these metal ions may significantly affect Aβ aggregation and deposition in the brain. While the effect of these metals on Aβ has been shown in vitro, there is less behavioral data supporting a direct role in cognitive impairment.

Alterations in fear response and spatial memory in pre- and post-natal zinc supplemented rats: remediation by copper.

The role of zinc in the nervous system is receiving increased attention. At a time when dietary fortification and supplementation have increased the amount of zinc being consumed, little work has been done on the effects of enhanced zinc on behavior. Both zinc and copper are essential trace minerals that are acquired from the diet; under normal conditions the body protects against zinc overload, but at excessive dosages, copper deficiency has been seen.

The effects of enhanced zinc on spatial memory and plaque formation in transgenic mice.

There is considerable evidence suggesting that metals play a central role in the pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals may both precipitate and potentiate an Alzheimer's disease phenotype. Despite this, there remain few studies that have examined the behavioral consequences of elevated dietary metals in wild type and Alzheimer's disease animals.

Evidence that the ZNT3 protein controls the total amount of elemental zinc in synaptic vesicles.

The ZNT3 protein decorates the presynaptic vesicles of central neurons harboring vesicular zinc, and deletion of this protein removes staining for zinc. However, it has been unclear whether only histochemically reactive zinc is lacking or if, indeed, total elemental zinc is missing from neurons lacking the Slc30a3 gene, which encodes the ZNT3 protein. The limitations of conventional histochemical procedures have contributed to this enigma.

Abnormal flash visual evoked potentials in malnourished infants: an evaluation using principal component analysis.

Objective: To characterize the morphology of flash visual evoked potentials (fVEPs) obtained from infants hospitalized with severe, chronic malnutrition (marasmus).

Methods: A covariance-based principal component analysis with Promax factor rotation was applied to fVEPs obtained from malnourished infants and age-matched control subjects.

Results: The analysis suggests the presence of a late positive complex in the fVEP, with at least one of its components being significantly diminished in marasmic infants.

High concentration of zinc in sub-retinal pigment epithelial deposits.

One of the hallmarks of age-related macular degeneration (AMD), the leading cause of blindness in the elderly in Western societies, is the accumulation of sub-retinal pigment epithelial deposits (sub-RPE deposits), including drusen and basal laminar deposits, in Bruch's membrane (BM). The nature and the underlying mechanisms of this deposit formation are not fully understood. Because we know that zinc contributes to deposit formation in neurodegenerative diseases, we tested the hypothesis that zinc might be involved in deposit formation in AMD.

Elemental mapping and quantitative analysis of Cu, Zn, and Fe in rat brain sections by laser ablation ICP-MS.

This report details the application of laser ablation quadrupole ICP-MS for the (multi)elemental mapping of 100-microm-thick sections of rat brain. The laser spot size used was 60 microm, and the laser scan speed was 120 microm s(-1). The analysis was relatively rapid, allowing mapping of a whole brain thin section (approximately 1 cm2) in about 2 h.