Effects of acute lying and sleep deprivation on metabolic and inflammatory responses of lactating dairy cows.

Dairy cows that are restricted from lying down have a reduced ability to sleep. In other species, sleep loss is a key risk factor for disease, mediated by changes in metabolic and inflammatory responses. The cumulative effect of lying and sleep deprivation on cow health is unknown. The objective was to determine the effects of lying and sleep deprivation on metabolic and inflammatory responses of dairy cows. Data were collected from 8 multiparous and 4 primiparous lactating cows (199 ± 44 d in milk, 77 ± 30 d pregnant; mean ± standard deviation) enrolled in a study using a crossover design. Each cow was exposed to 2 treatments meant to induce sleep loss: (1) human disturbance (imposed by researchers making noise or physical contact when the cow's posture suggested sleep) and (2) lying deprivation (imposed by a wooden grid placed on the pen floor). Cows experienced a 24-h baseline period (d -1) followed by a 24-h treatment period (d 0), with a 12-d washout period between treatments. Baseline and treatment periods were imposed from 2100 to 2059 h. Cows were housed in individual pens during the acclimation period (d -3 and -2), d -1, and d 0. Nonesterified fatty acid and glucose concentrations were measured at 0300, 0900, 1500, and 2059 h on d -1 and 0. Proinflammatory cytokine mRNA [tumor necrosis factor (TNF), interleukin-1B (IL1B), and interleukin-6 (IL6)] abundance in whole-blood leukocytes, both nonstimulated and stimulated with lipopolysaccharide, were assessed at 2059 h on d -1 (end of baseline) and d 0 (end of treatment). Nonesterified fatty acids and glucose varied by time of day but were not affected by treatment or day. The abundances of TNF and IL1B from both stimulated and nonstimulated cells were higher following 24 h of lying deprivation (d 0) compared with baseline (d -1). Abundance of IL6 was increased in nonstimulated cells after lying deprivation compared with baseline. In contrast, human disturbance for 24 h did not alter TNF, IL1B, or IL6 abundance relative to baseline levels. These results suggest that a short period of lying deprivation generally increases inflammatory responses but not metabolic responses.

Enhancing the get healthy information and coaching service for Aboriginal adults: evaluation of the process and impact of the program.

BACKGROUND: Non-communicable chronic diseases in Australia contribute to approximately 85% of the total burden of disease; this proportion is greater for Aboriginal communities. The Get Healthy Service (GHS) is effective at reducing lifestyle-based chronic disease risk factors among adults and was enhanced to facilitate accessibility and ensure Aboriginal cultural appropriateness. The purpose of this study is to detail how formative research with Aboriginal communities was applied to guide the development and refinement of the GHS and referral pathways; and to assess the reach and impact of the GHS (and the Aboriginal specific program) on the lifestyle risk factors of Aboriginal participants. METHODS: Formative research included interviews with Aboriginal participants, leaders and community members, healthcare professionals and service providers to examine acceptability of the GHS; and contributed to the redesign of the GHS Aboriginal program. A quantitative analysis employing a pre-post evaluation design examined anthropometric measures, physical activity and fruit and vegetable consumption of Aboriginal participants using descriptive and chi square analyses, t-tests and Wilcoxon signed-rank tests. RESULTS: Whilst feedback from the formative research was positive, Aboriginal people identified areas for service enhancement, including improving program content, delivery and service promotion as well as ensuring culturally appropriate referral pathways. Once these changes were implemented, the proportion of Aboriginal participants increased significantly (3.2 to 6.4%). There were significant improvements across a number of risk factors assessed after six months (average weight loss: 3.3 kg and waist circumference reduction: 6.2 cm) for Aboriginal participants completing the program. CONCLUSIONS: Working in partnership with Aboriginal people, Elders, communities and peak bodies to enhance the GHS for Aboriginal people resulted in an enhanced culturally acceptable and tailored program which significantly reduced chronic disease risk factors for Aboriginal participants. Mainstream telephone based services can be modified and enhanced to meet the needs of Aboriginal communities through a process of consultation, community engagement, partnership and governance.

Development of a noninvasive system for monitoring dairy cattle sleep.

Limited research has been conducted to assess sleep in production livestock primarily because of limitations with monitoring capabilities. Consequently, biological understanding of production circumstances and facility options that affect sleep is limited. The objective of this study was to assess if data collected from a proof-of-concept, noninvasive 3-axis accelerometer device are correlated with sleep and wake-like behaviors in dairy cattle. Four Holstein dairy cows housed at the University of Kentucky Coldstream Dairy in September 2013 were visually observed for 2 consecutive 24-h periods. The accelerometer device was attached to a harness positioned on the right side of each cow's neck. Times of classified behaviors of wake (standing, head up, alert, eyes open) or sleep-like behaviors (lying, still, head resting on ground, eyes closed) were recorded continuously by 2 observers who each watched 2 cows at a time. The radial signal was extracted from 3 different axes of the accelerometer to obtain a motion signal independent of direction of movement. Radial signal features were examined for maximizing the performance of detecting sleep-like behaviors using a Fisher's linear discriminant analysis classifier. The study included 652min of high-activity wake behaviors and 107min of sleep-like behavior among 4 cows. Results from a bootstrapping analysis showed an agreement between human observation and the linear discriminant analysis classifier, with an accuracy of 93.7±0.7% for wake behavior and 92.2±0.8% for sleep-like behavior (±95% confidence interval).This prototype shows promise in measuring sleep-like behaviors. Improvements to both hardware and software should allow more accurate determinations of subtle head movements and respiratory movements that will further improve the assessment of these sleep-like behaviors, including estimates of deep, light, and rapid eye movement sleep. These future studies will require simultaneous electroencephalography and electromyography measures and perhaps additional measures of arousal thresholds to validate this system for measuring true sleep.

Evaluating the effectiveness of an Australian obesity mass-media campaign: how did the 'Measure-Up' campaign measure up in New South Wales?

In 2008, the Australian Government launched a mass-media campaign 'Measure-Up' to reduce lifestyle-related chronic disease risk. Innovative campaign messages linked waist circumference and chronic disease risk. Communication channels for the campaign included television, press, radio and outdoor advertising and local community activities. This analysis examines the impact of the campaign in the state of New South Wales, Australia. Cross-sectional telephone surveys (n = 1006 adults pre- and post-campaign) covered self-reported diet and physical activity, campaign awareness, knowledge about waist circumference, personal relevance of the message, perceived confidence to make lifestyle changes and waist-measuring behaviours. The campaign achieved high unprompted (38%) and prompted (89%) awareness. From pre- to post-campaign, knowledge and personal relevance of the link between waist circumference and chronic disease and waist measuring behaviour increased, although there were no significant changes in reported fruit and vegetable intake nor in physical activity. Knowledge of the correct waist measurement threshold for chronic disease risk increased over 5-fold, adjusted for demographic characteristics. 'Measure-Up' was successful at communicating the new campaign messages. Continued long-term investment in campaigns such as 'Measure-Up', supplemented with community-based health promotion, may contribute to population risk factor understanding and behaviour change to reduce chronic disease.

Chronic Fragmentation of the Daily Sleep-Wake Rhythm Increases Amyloid-beta Levels and Neuroinflammation in the 3xTg-AD Mouse Model of Alzheimer's Disease.

Fragmentation of the daily sleep-wake rhythm with increased nighttime awakenings and more daytime naps is correlated with the risk of development of Alzheimer's disease (AD). To explore whether a causal relationship underlies this correlation, the present study tested the hypothesis that chronic fragmentation of the daily sleep-wake rhythm stimulates brain amyloid-beta (Aß) levels and neuroinflammation in the 3xTg-AD mouse model of AD. Female 3xTg-AD mice were allowed to sleep undisturbed or were subjected to chronic sleep fragmentation consisting of four daily sessions of enforced wakefulness (one hour each) evenly distributed during the light phase, five days a week for four weeks. Piezoelectric sleep recording revealed that sleep fragmentation altered the daily sleep-wake rhythm to resemble the pattern observed in AD. Levels of amyloid-beta (Aß40 and Aß42) determined by ELISA were higher in hippocampal tissue collected from sleep-fragmented mice than from undisturbed controls. In contrast, hippocampal levels of tau and phospho-tau differed minimally between sleep fragmented and undisturbed control mice. Sleep fragmentation also stimulated neuroinflammation as shown by increased expression of markers of microglial activation and proinflammatory cytokines measured by q-RT-PCR analysis of hippocampal samples. No significant effects of sleep fragmentation on Aß, tau, or neuroinflammation were observed in the cerebral cortex. These studies support the concept that improving sleep consolidation in individuals at risk for AD may be beneficial for slowing the onset or progression of this devastating neurodegenerative disease.

Human embryonic stem cell-derived oligodendrocyte progenitor cells express the serotonin receptor and are susceptible to JC virus infection.

We studied the susceptibility of human embryonic stem cell-derived oligodendrocyte progenitor cells to infection with JC virus, the causative agent of progressive multifocal leukoencephalopathy (PML). A human embryonic stem cell line, H7, was used to derive an enriched population of cells expressing the oligodendrocyte progenitor cell-specific marker NG2. These cells expressed the 5HT2a receptor (5HT2aR) for JC virus and were highly susceptible to infection. Infection was reduced by treatment with anti-5HT2aR antibodies and by the 5HT2aR antagonists ritanserin and ketanserin. This is the first demonstration that human embryonic stem cell-derived oligodendrocyte progenitor cells are susceptible to JC virus infection and indicates that cells poised to replenish mature oligodendrocytes in PML lesions may also be a target of viral infection.

Evolutionarily conserved function of a viral microRNA.

MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most of unknown function. The majority of viral miRNAs are not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocompromised individuals, JC virus and BK virus, encode miRNAs with the same function as that of the monkey polyomavirus simian virus 40 miRNAs. These miRNAs are expressed late during infection to autoregulate early gene expression. We show that the miRNAs generated from both arms of the pre-miRNA hairpin are active at directing the cleavage of the early mRNAs. This finding suggests that despite multiple differences in the miRNA seed regions, the primary target (the early mRNAs) and function (the downregulation of early gene expression) are evolutionarily conserved among the primate polyomavirus-encoded miRNAs. Furthermore, we show that these miRNAs are expressed in individuals diagnosed with polyomavirus-associated disease, suggesting their potential as targets for therapeutic intervention.

Interferon beta1-a and selective anti-5HT(2a) receptor antagonists inhibit infection of human glial cells by JC virus.

JC virus (JCV) is the causative agent of progressive multifocal leukoenchaphalopathy (PML). The disease develops when JCV gains access to the central nervous system, infects and destroys oligodendrocytes. The disease is rapidly progressing, typically fatal and no effective therapies exist to treat or prevent PML. The recent occurrence of PML in multiple sclerosis patients being treated with Avonex (IFNbeta1-a) and Tysabri (Natalizumab) and the recent reports linking JCV infection to the 5HT(2a) serotonin receptor led us to evaluate the effects of IFNbeta1-a and a panel of 5HT(2a) receptor antagonists for their ability to modulate virus infection. IFNbeta1-a was found to be a potent inhibitor of both virus infection and viral early and late gene expression. In addition, several 5HT(2a) receptor antagonists inhibited initial infection of cells by JCV but were less effective at reducing viral loads in an already established infection.

ATP induces large quaternary rearrangements in a cage-like chaperonin structure.

BACKGROUND: The chaperonins, a family of molecular chaperones, are large oligomeric proteins that bind nonnative intermediates of protein folding. They couple the release and correct folding of their ligands to the binding and hydrolysis of ATP. Chaperonin 60 (cpn60) is a decatetramer (14-mer) of 60 kD subunits. Folding of some ligands also requires the cooperation of cpn10, a heptamer of 10 kD subunits. RESULTS: We have determined the three-dimensional arrangements of subunits in Rhodobacter sphaeroides cpn60 in the nucleotide-free and ATP-bound forms. Negative stain electron microscopy and tilt reconstruction show the cylindrical structure of the decatetramer comprising two rings of seven subunits. The decatetramer consists of two cages joined base-to-base without a continuous central channel. These cages appear to contain bound polypeptide with an asymmetric distribution between the two rings. The two major domains of each subunit are connected on the exterior of the cylinder by a narrower bridge of density that could be a hinge region. Binding of ATP to cpn60 causes a major rearrangement of the protein density, which is reversed upon the hydrolysis of the ATP. Cpn10 binds to only one end of the cpn60 structure and is visible as an additional layer of density forming a cap on one end of the cpn60 cylinder. CONCLUSIONS: The observed rearrangement is consistent with an inward 5-10 degrees rotation of subunits, pivoting about the subunit contacts between the two heptamers, and thus bringing cpn60 domains towards the position occupied by the bound polypeptide. This change could explain the stimulation of ATPase activity by ligands, and the effects of ATP on lowering the affinity of cpn60 for ligands and on triggering the release of folding polypeptides.

Levels of fos, ets2, and myb proto-oncogene RNAs correlate with segregation of chromosome 11 of normal cells and with suppression of tumorigenicity in human cell hybrids.

The tumorigenicity in nude mice of human carcinoma-derived D98AH2 (D98) cells is suppressed when cell hybrids are made by fusing these cells with normal human diploid cells. Selection for hybrids that have segregated chromosomes results in the recovery of tumorigenic segregants. These segregants have all lost at least one copy of chromosome 11 of the diploid cell parent. Earlier we found that the parental D98 cells had detectable levels of mRNA specific for 13 of 21 proto-oncogenes examined. To determine if transregulation of proto-oncogenes by genes of the normal cell occurs in such hybrids, the steady-state levels of mRNA specific to 22 proto-oncogenes in the parental cells were compared with those of nontumorigenic D98 X human diploid hybrids as well as with those of their tumorigenic segregants and with the cells of the resulting tumors. The only chromosome consistently segregated in the latter was chromosome 11 of the diploid cell. fos and ets2 RNA levels and the amount of fos protein were consistently elevated in the segregants compared with amounts in the original hybrids. An unexpected finding was the inverse relationship for myb RNA that was barely detected in the parental D98 cells but was at least 10-fold elevated in hybrids that did not have segregated chromosomes compared with those that did. These patterns were evident in RNAs prepared from both subconfluent and confluent cell cultures. The findings suggest that genes of the normal cell parent can affect proto-oncogene expression. Whether the genes affecting fos, ets2, and myb RNA levels are on chromosome 11 and whether these alterations are causally related to the tumorigenic phenotype of the hybrid remain to be determined.

A glycosylation-deficient endothelial cell mutant with modified responses to transforming growth factor-beta and other growth inhibitory cytokines: evidence for multiple growth inhibitory signal transduction pathways.

An endothelial cell line (M40) resistant to growth inhibition by transforming growth factor-beta type 1 (TGF beta 1) was isolated by chemical mutagenesis and growth in the presence of TGF beta 1. Like normal endothelial cells, this mutant is characterized by high expression of type II TGF beta receptor and low expression of type I TGF beta receptor. However, the mutant cells display a type II TGF beta receptor of reduced molecular weight as a result of a general defect in N-glycosylation of proteins. The alteration does not impair TGF beta 1 binding to cell surface receptors or the ability of TGF beta 1 to induce fibronectin or plasminogen activator inhibitor-type I production. M40 cells were also resistant to growth inhibition by tumor necrosis factor alpha (TNF alpha) and interleukin-1 alpha (IL-1 alpha) but were inhibited by interferon-gamma (IFN gamma) and heparin. These results imply that TGF beta 1, TNF alpha, and IL-1 alpha act through signal transducing pathways that are separate from pathways for IFN gamma and heparin. Basic fibroblast growth factor was still mitogenic for M40, further suggesting that TGF beta 1, TNF alpha, and IL-1 alpha act by direct inhibition of cell growth rather than by interfering with growth stimulatory pathways.

Mechanism of activation of human ras genes cloned from a gastric adenocarcinoma and a pancreatic carcinoma cell line.

We have analyzed the mechanism of activation of two human ras oncogenes. We have also identified a rasN gene from a human gastric adenocarcinoma which efficiently induced both morphological transformation and tumorigenicity of NIH3T3 cells in a transfection assay. The rasN gene in tumor tissue DNA did not appear to be rearranged or amplified. A molecular clone, which contained an EcoRI fragment spanning the first and second rasN exons, was molecularly cloned directly from the human tumor DNA. Chimeric constructions and DNA sequencing defined the mechanism of activation of the gene as a mutation in the 61st amino acid codon substituting arginine for glutamine. Normal DNA isolated from Epstein-Barr virus immortalized lymphocytes derived from the same patient did not induce morphological transformation or tumorigenicity in NIH3T3 cells. A cloned cell line isolated from the human pancreatic carcinoma cell line Panc1 had previously been shown to contain an activated rasK-2. Sequence analysis of the cloned transfected gene reveals a G to A change within codon 12, which is presumably responsible for its biological activity. This represents the first identification of a codon 12 aspartic acid substitution of a c-rask oncogene from a human tumor-derived cell line.

A threshold effect in the induction of tumorigenicity of an established human cell line by v-mos.

The nontumorigenic immortal human cell line, SV80, was transfected with the v-mos gene to assess the gene's effect on tumorigenicity of cultured human cells. Two classes of cells, each containing functional v-mos, were obtained. The first class contained low levels of v-mos RNA, was morphologically transformed, but was nontumorigenic in nude mice. The second was also morphologically transformed, but contained high levels of v-mos RNA and was tumorigenic. The results indicate that SV80 cells behave similarly to murine fibroblasts in their response to v-mos in that they can be rendered tumorigenic by the viral oncogene. However, tumorigenicity was effected through a mechanism which involves different threshold doses for morphologic and tumorigenic transformation.

Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2.

Human metastasis-suppressor genes nm23-1 (NME1) and nm23-2 (NME2) are implicated in control of the metastatic potential of malignant cells. Using somatic cell hybrid analysis and fluorescence in situ hybridization we co-localized both genes to 17q21.3. The 17q21 region carries the locus responsible for early-onset familial breast-ovarian cancer and several other genes that are involved in tumorigenesis and differentiation and undergo frequent rearrangements during neoplastic development. Thus, our mapping places the NME genes in a region that may be subjected to multiple selection pressures. NME1 and NME2 genes were expressed as soluble proteins in a T7 bacterial expression system. Both proteins are independently active nucleotide diphosphate kinases and readily form intra- and intermolecular disulfide bonds. The biochemical properties of these proteins may explain the diversity of mature eucaryotic nucleoside diphosphate kinases.

Acetylcholine becomes the major excitatory neurotransmitter in the hypothalamus in vitro in the absence of glutamate excitation.

Glutamate and GABA are two major fast neurotransmitters (excitatory and inhibitory, respectively) in the CNS, including the hypothalamus. They play a key role in the control of excitation/inhibition balance and determine the activity and excitability of neurons in many neuronal circuits. Using neuronal cultures, whole-cell recording, Ca(2+) imaging, and Northern blots, we studied the compensatory regulation of neuronal activity during a prolonged decrease in glutamate excitation. We report here that after a chronic (6-17 d) blockade of ionotropic glutamate receptors, neurons in hypothalamic cultures revealed excitatory electrical and Ca(2+) synaptic activity, which was not elicited in the control cultures that were not subjected to glutamate blockade. This activity was suppressed with acetylcholine (ACh) receptor antagonists and was potentiated by eserine, an inhibitor of acetylcholinesterase, suggesting its cholinergic nature. The upregulation of ACh receptors and the contribution of ACh to the control of the excitation/inhibition balance in cultures after a prolonged decrease in glutamate activity were also demonstrated. Enhanced ACh transmission was also found in chronically blocked cerebellar but not cortical cultures, suggesting the region-specific character of glutamate-ACh interactions in the brain. We believe that in the absence of glutamate excitation in the hypothalamus in vitro, ACh, a neurotransmitter normally exhibiting only weak activity in the hypothalamus, becomes the major excitatory neurotransmitter and supports the excitation/inhibition balance. The increase in excitatory ACh transmission during a decrease in glutamate excitation may represent a novel form of neuronal plasticity that regulates activity and excitability of neurons during the glutamate/GABA imbalance.

Gene expression in the brain across the hibernation cycle.

The purpose of this study was to characterize changes in gene expression in the brain of a seasonal hibernator, the golden-mantled ground squirrel, Spermophilus lateralis, during the hibernation season. Very little information is available on molecular changes that correlate with hibernation state, and what has been done focused mainly on seasonal changes in peripheral tissues. We produced over 4000 reverse transcription-PCR products from euthermic and hibernating brain and compared them using differential display. Twenty-nine of the most promising were examined by Northern analysis. Although some small differences were observed across hibernation states, none of the 29 had significant changes. However, a more direct approach, investigating expression of putative hibernation-responsive genes by Northern analysis, revealed an increase in expression of transcription factors c-fos, junB, and c-Jun, but not junD, commencing during late torpor and peaking during the arousal phase of individual hibernation bouts. In contrast, prostaglandin D2 synthase declined during late torpor and arousal but returned to a high level on return to euthermia. Other genes that have putative roles in mammalian sleep or specific brain functions, including somatostatin, enkephalin, growth-associated protein 43, glutamate acid decarboxylases 65/67, histidine decarboxylase, and a sleep-related transcript SD464 did not change significantly during individual hibernation bouts. We also observed no decline in total RNA or total mRNA during torpor; such a decline had been previously hypothesized. Therefore, it appears that the dramatic changes in body temperature and other physiological variables that accompany hibernation involve only modest reprogramming of gene expression or steady-state mRNA levels.

A pentameric form of human serum amyloid P component. Crystallization, X-ray diffraction and neutron scattering studies.

Human serum amyloid P component crystallizes from sodium acetate buffer (pH 5.5) in the presence of calcium and polyethylene glycol 6000, at 4 degrees C. The space group is P2(1) and the cell parameters are a = 69.0 A (1 A = 0.1 nm), b = 99.3 A, c = 96.8 A, beta = 96.1. Density considerations supported by neutron scattering and gel filtration experiments indicate that the species crystallized is pentameric. The orientation of the pentamer 5-fold axis is determined and a crystal packing for the discs is proposed.

Genetic vulnerability to drug abuse. The D2 dopamine receptor Taq I B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers.

Alcoholics are more likely than nonalcoholics to display the Taq I A1 restriction fragment length polymorphism of the D2 dopamine receptor gene, according to four of six studies that examined alcoholics and controls. The current study examines whether the association observed in alcoholism might extend to other addictive substances by examining D2 dopamine receptor Taq I A and B restriction fragment length polymorphisms in polysubstance users and controls free of significant substance use. We hypothesized a stronger association for the B1 restriction fragment length polymorphism since it lies closer to dopamine receptor protein coding and 5' regulatory regions. Heavy polysubstance users and subjects with DSM-III-R psychoactive substance use diagnoses displayed significantly higher Taq I B1 frequencies than control subjects; Taq I A1 results for these comparisons were less robust. These results are consistent with a role for a D2 dopamine receptor gene variant marked by these restriction fragment length polymorphisms in enhanced substance abuse vulnerability.

Characterization of the circadian system of NGFI-A and NGFI-A/NGFI-B deficient mice.

The genes NGFI-A (also known as EGR-1, zif/268, and Krox-24) and NGFI-B (nur/77) have previously been shown to be induced in the SCN of rats and hamsters by photic stimulation during the subjective night. The purpose of this study is to determine whether these genes are also induced in the SCN of mice and, if so, to characterize the circadian system of animals in which either NGFI-A or both NGFI-A and NGFI-B were eliminated by homologous recombination. In wildtype mice, NGFI-A mRNA was found to be induced in the SCN as in other rodent species. Therefore, wheel-running activity was recorded from null mutants and wildtype controls under LD 12:12 and DD conditions. Mice of all three strains appeared to entrain normally to LD 12:12 and could re-entrain to both phase advances and phase delays of the light cycle. The response of the circadian pacemaker of all three genotypes to acute light pulses appeared to be normal. The retinal innervation of the SCN in NGFI-A-/- mice and the photic induction of Fos in the SCN of both NGFI-A-/- and NGFI-A-/-/B-/- mice were indistinguishable from wildtype mice. These results indicate that induction of NGFI-A and NGFI-B is not required for photic entrainment or phase shifting of the mouse circadian system.

Increased fragmentation of sleep-wake cycles in the 5XFAD mouse model of Alzheimer's disease.

Sleep perturbations including fragmented sleep with frequent night-time awakenings and daytime naps are common in patients with Alzheimer's disease (AD), and these daily disruptions are a major factor for institutionalization. The objective of this study was to investigate if sleep-wake patterns are altered in 5XFAD mice, a well-characterized double transgenic mouse model of AD which exhibits an early onset of robust AD pathology and memory deficits. These mice have five distinct human mutations in two genes, the amyloid precursor protein (APP) and Presenilin1 (PS1) engineered into two transgenes driven by a neuron-specific promoter (Thy1), and thus develop severe amyloid deposition by 4 months of age. Age-matched (4-6.5 months old) male and female 5XFAD mice were monitored and compared to wild-type littermate controls for multiple sleep traits using a non-invasive, high throughput, automated piezoelectric system which detects breathing and gross body movements to characterize sleep and wake. Sleep-wake patterns were recorded continuously under baseline conditions (undisturbed) for 3 days and after sleep deprivation of 4h, which in mice produces a significant sleep debt and challenge to sleep homeostasis. Under baseline conditions, 5XFAD mice exhibited shorter bout lengths (14% lower values for males and 26% for females) as compared to controls (p<0.001). In females, the 5XFAD mice also showed 12% less total sleep than WT (p<0.01). Bout length reductions were greater during the night (the active phase for mice) than during the day, which does not model the human condition of disrupted sleep at night (the inactive period). However, the overall decrease in bout length suggests increased fragmentation and disruption in sleep consolidation that may be relevant to human sleep. The 5XFAD mice may serve as a useful model for testing therapeutic strategies to improve sleep consolidation in AD patients.