Degradation of Bone Quality in a Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) patients present with symptoms such as impairment of insulin signaling, chronic inflammation, and oxidative stress. Furthermore, there are comorbidities associated with AD progression. For example, osteoporosis is common with AD wherein patients exhibit reduced mineralization and a risk for fragility fractures.

Robust light-dark patterns and reduced amyloid load in an Alzheimer's disease transgenic mouse model.

Circadian disruption resulting from exposure to irregular light-dark patterns and sleep deprivation has been associated with beta amyloid peptide (Aβ) aggregation, which is a major event in Alzheimer's disease (AD) pathology. We exposed 5XFAD mice and littermate controls to dim-light vs. bright-light photophases to investigate the effects of altering photophase strength on AD-associated differences in cortical Aβ42 levels, wheel-running activity, and circadian free-running period (tauDD).

Exposure to Lead (Pb) Eliminates Avoidance of Pb-Treated Oviposition Substrates in a Dose-Dependent Manner in Female Vinegar Flies.

Female vinegar flies (Drosophila melanogaster) preferentially oviposit eggs on oviposition substrates that decrease larval foraging costs. We tested whether female D. melanogaster would avoid oviposition substrates containing lead (Pb), which could potentially decrease offspring fitness.

Intraspecific Genetic Variation for Lead-Induced Changes in Reproductive Strategies.

We aimed to identify genetic variation in the response of reproductive behaviors to lead (Pb) exposure. We reared a subset of the Drosophila Genetic Reference Panel (DGRP) inbred lines on control or Pb-treated (500 μM PbAc) medium and tested for differences in copulation latency, copulation duration, and fecundity. Pb exposure decreased fecundity (p < 0.

The mutation impairs circadian locomotor activity.

We investigated effects of mutation ap on circadian locomotor activity, eclosion rhythms, and transcript levels of and in . We investigated circadian locomotor activity and eclosion rhythms in and wild-type flies, their F1 and F2 offspring, and wingless mutants and show that disrupts circadian locomotor rhythms in a genetically recessive manner, that is not caused by the absence of wings. The strain also showed impaired circadian activity rhythms, providing independent evidence for a significant role of in circadian locomotor rhythm expression.

Asymmetrical positive assortative mating induced by developmental lead (Pb) exposure in a model system, .

Anthropogenic pollutants have the potential to disrupt reproductive strategies. Little is known about how lead (Pb) exposure disrupts individual-level responses in reproductive behaviors, which are important for fitness. was used as a model system to determine the effects of: 1) developmental lead exposure on pre-mating reproductive behaviors (i.

Long term rebaudioside A treatment does not alter circadian activity rhythms, adiposity, or insulin action in male mice.

Obesity is a major public health problem that is highly associated with insulin resistance and type 2 diabetes, two conditions associated with circadian disruption. To date, dieting is one of the only interventions that result in substantial weight loss, but restricting caloric intake is difficult to maintain long-term. The use of artificial sweeteners, particularly in individuals that consume sugar sweetened beverages (energy drinks, soda), can reduce caloric intake and possibly facilitate weight loss.

Accumulation, elimination, sequestration, and genetic variation of lead (Pb) loads within and between generations of Drosophila melanogaster.

We examined accumulation, sequestration, elimination, and genetic variation for lead (Pb) loads within and between generations of Drosophila melanogaster. Flies were reared in control or leaded medium at various doses and tested for their Pb loads at different stages of development (larvae, eclosion, newly-eclosed adults, and mature adults). Pb loads were tested using Inductively Coupled Plasma Mass Spectrometry (ICP-MS).

The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer's disease.

Circadian behavioural deficits, including sleep irregularity and restlessness in the evening, are a distressing early feature of Alzheimer's disease (AD). We have investigated these phenomena by studying the circadian behaviour of transgenic Drosophila expressing the amyloid beta peptide (Aβ). We find that Aβ expression results in an age-related loss of circadian behavioural rhythms despite ongoing normal molecular oscillations in the central clock neurons.

Larval ethanol exposure alters free-running circadian rhythm and per Locus transcription in adult D. melanogaster period mutants.

Alcohol consumption causes disruptions in a variety of daily rhythms, including the circadian free-running rhythm. A previous study conducted in our laboratories has shown that larval ethanol exposure alters the free-running period in adult Canton-S Drosophila melanogaster. Few studies, however, have explored the effect of alcohol exposure on organisms exhibiting circadian periods radically different than (normal) 24-h.

Drosophila melanogaster as a model for lead neurotoxicology and toxicogenomics research.

Drosophila melanogaster is an excellent model animal for studying the neurotoxicology of lead. It has been known since ancient Roman times that long-term exposure to low levels of lead results in behavioral abnormalities, such as what is now known as attention deficit hyperactivity disorder (ADHD). Because lead alters mechanisms that underlie developmental neuronal plasticity, chronic exposure of children, even at blood lead levels below the current CDC community action level (10 μg/dl), can result in reduced cognitive ability, increased likelihood of delinquency, behaviors associated with ADHD, changes in activity level, altered sensory function, delayed onset of sexual maturity in girls, and changes in immune function.

Larval ethanol exposure alters adult circadian free-running locomotor activity rhythm in Drosophila melanogaster.

Alcohol consumption causes disruptions in a variety of daily rhythms, including the sleep-wake cycle. Few studies have explored the effect of alcohol exposure only during developmental stages preceding maturation of the adult circadian clock, and none have examined the effects of alcohol on clock function in Drosophila. This study investigates developmental and behavioral correlates between larval ethanol exposure and the adult circadian clock in Drosophila melanogaster, a well-established model for studying circadian rhythms and effects of ethanol exposure.

Changes in circadian rhythms during puberty in Rattus norvegicus: developmental time course and gonadal dependency.

During puberty, humans develop a later chronotype, exhibiting a phase-delayed daily rest/activity rhythm. The purpose of this study was to determine: 1) whether similar changes in chronotype occur during puberty in a laboratory rodent species, 2) whether these changes are due to pubertal hormones affecting the circadian timekeeping system. We tracked the phasing and distribution of wheel-running activity rhythms during post-weaning development in rats that were gonadectomized before puberty or left intact.

Pb2+: an endocrine disruptor in Drosophila?

Environmental exposure to Pb(2+) affects hormone-mediated responses in vertebrates. To help establish the fruit fly, Drosophila melanogaster, as a model system for studying such disruption, we describe effects of Pb(2+) on hormonally regulated traits. These include duration of development, longevity, females' willingness to mate, fecundity and adult locomotor activity.

Genetical toxicogenomics in Drosophila identifies master-modulatory loci that are regulated by developmental exposure to lead.

The genetics of gene expression in recombinant inbred lines (RILs) can be mapped as expression quantitative trait loci (eQTLs). So-called "genetical genomics" studies have identified locally acting eQTLs (cis-eQTLs) for genes that show differences in steady-state RNA levels. These studies have also identified distantly acting master-modulatory trans-eQTLs that regulate tens or hundreds of transcripts (hotspots or transbands).

Genetic aspects of behavioral neurotoxicology.

Considerable progress has been made over the past couple of decades concerning the molecular bases of neurobehavioral function and dysfunction. The field of neurobehavioral genetics is becoming mature. Genetic factors contributing to neurologic diseases such as Alzheimer's disease have been found and evidence for genetic factors contributing to other diseases such as schizophrenia and autism are likely.

Variations at a quantitative trait locus (QTL) affect development of behavior in lead-exposed Drosophila melanogaster.

We developed Drosophila melanogaster as a model to study correlated behavioral, neuronal and genetic effects of the neurotoxin lead, known to affect cognitive and behavioral development in children. We showed that, as in vertebrates, lead affects both synaptic development and complex behaviors (courtship, fecundity, locomotor activity) in Drosophila. By assessing differential behavioral responses to developmental lead exposure among recombinant inbred Drosophila lines (RI), derived from parental lines Oregon R and Russian 2b, we have now identified a genotype by environment interaction (GEI) for a behavioral trait affected by lead.

Effects of anabolic androgenic steroids on the development and expression of running wheel activity and circadian rhythms in male rats.

In humans, anabolic androgenic steroid (AAS) use has been associated with hyperactivity and disruption of circadian rhythmicity. We used an animal model to determine the impact of AAS on the development and expression of circadian function. Beginning on day 68 gonadally intact male rats received testosterone, nandrolone, or stanozolol via constant release pellets for 60 days; gonadally intact controls received vehicle pellets.

Additivity in murine circadian phototransduction.

Additivity in the circadian phototransduction system of the mouse has not been tested directly. Because of this, accurate prediction of circadian phase shifts elicited by polychromatic light stimuli cannot be derived from the results of studies using monochromatic light stimuli. This limitation also makes it impossible to deduce the relative contributions of the photoreceptive mechanisms (rods, cones and melanopsin-containing retinal ganglion cells) underlying circadian phototransduction in the mouse.

Effects of withdrawal from anabolic androgenic steroids on aggression in adult male rats.

In gonadally intact male rats, chronic exposure to high levels of testosterone propionate (TP) increases aggression, nandrolone (ND) has little effect and stanozolol (ST) suppresses aggression. The present experiment tested whether the effects of TP, ND and ST on aggression and reproductive tissues are reversed following anabolic androgenic steroid (AAS) withdrawal. Gonadally intact males received TP, ND, ST or vehicle for 12 weeks.

Physical provocation potentiates aggression in male rats receiving anabolic androgenic steroids.

Anabolic androgenic steroids (AAS) have been linked to indiscriminant and unprovoked aggression and violence. We employed a brief tail pinch to examine the effects of different AAS on intermale aggression in gonadally intact male rats in response to a mild physical provocation. Animals received 5 mg/kg testosterone propionate (TP), nandrolone (ND), or stanozolol (ST) 5 days/week.

Aggression in male rats receiving anabolic androgenic steroids: effects of social and environmental provocation.

This study examined the effects of anabolic androgenic steroids (AAS) on aggression under different social and environmental conditions. Three AAS were tested in gonadally intact male rats: testosterone propionate (TP), nandrolone (ND), and stanozolol (ST). Doses of 5 mg/kg were given 5 times/week, with gonadally intact controls receiving vehicle only (propylene glycol).