Altered circadian behavior and light sensing in mouse models of Alzheimer's disease.

Circadian symptoms have long been observed in Alzheimer's disease (AD) and often appear before cognitive symptoms, but the mechanisms underlying circadian alterations in AD are poorly understood. We studied circadian re-entrainment in AD model mice using a "jet lag" paradigm, observing their behavior on a running wheel after a 6 h advance in the light:dark cycle. Female 3xTg mice, which carry mutations producing progressive amyloid beta and tau pathology, re-entrained following jet lag more rapidly than age-matched wild type controls at both 8 and 13 months of age.

Altered circadian behavior and light sensing in mouse models of Alzheimer's disease.

Circadian symptoms have long been observed in Alzheimer's disease (AD) and often appear before cognitive symptoms, but the mechanisms underlying circadian alterations in AD are poorly understood. We studied circadian re-entrainment in AD model mice using a "jet lag" paradigm, observing their behavior on a running wheel after a six hour advance in the light:dark cycle. Female 3xTg mice, which carry mutations producing progressive amyloid beta and tau pathology, re-entrained following jet lag more rapidly than age-matched wild type controls at both 8 and 13 months of age.

Oxidized cholesterol species as signaling molecules in the brain: diabetes and Alzheimer's disease.

Type 2 diabetes is associated with adverse central nervous system effects, including a doubled risk for Alzheimer's disease (AD) and increased risk of cognitive impairment, but the mechanisms connecting diabetes to cognitive decline and dementia are unknown. One possible link between these diseases may be the associated alterations to cholesterol oxidation and metabolism in the brain. We will survey evidence demonstrating alterations to oxysterols in the brain in AD and diabetes and how these oxysterols could contribute to pathology, as well as identifying research questions that have not yet been addressed to allow for a fuller understanding of the role of oxysterols in AD and diabetes.

Insulin resistance and impaired lipid metabolism as a potential link between diabetes and Alzheimer's disease.

Diabetes disrupts organs throughout the body including the brain. Evidence suggests diabetes is a risk factor for Alzheimer's disease (AD) and neurodegeneration. In this review, we focus on understanding how diabetes contributes to the progression of neurodegeneration by influencing several aspects of the disease process.

The Behavioral Sequelae of Social Defeat Require Microglia and Are Driven by Oxidative Stress in Mice.

Chronic social defeat (CSD) in male mice can produce anxiety and aberrant socialization. Animals susceptible to CSD show activation of microglia, which have elevated levels of oxidative stress markers. We hypothesized that microglia and reactive oxygen species (ROS) production contribute to the CSD stress-induced changes in affective behavior.

Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility.

An animal's ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brain's immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglia were isolated and analyzed by microarray. Microglia transcriptomes from CSD-S mice were enriched for pathways associated with inflammation, phagocytosis, oxidative stress, and extracellular matrix remodeling.

Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism.

Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome-immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood.

Chronic social defeat reduces myelination in the mouse medial prefrontal cortex.

The medial prefrontal cortex (mPFC) plays a key role in top-down control of the brain's stress axis, and its structure and function are particularly vulnerable to stress effects, which can lead to depression in humans and depressive-like states in animals. We tested whether chronic social defeat produces structural alterations in the mPFC in mice. We first performed a microarray analysis of mPFC gene expression changes induced by defeat, and biological pathway analysis revealed a dominant pattern of down-regulation of myelin-associated genes.