Phospholipid profiling of plasma from GW veterans and rodent models to identify potential biomarkers of Gulf War Illness.

Gulf War Illness (GWI), which affects at least one fourth of the 700,000 veterans deployed to the Gulf War (GW), is characterized by persistent and heterogeneous symptoms, including pain, fatigue and cognitive problems. As a consequence, this illness remains difficult to diagnose. Rodent models have been shown to exhibit different symptomatic features of GWI following exposure to particular GW agents (e.

EFAD transgenic mice as a human relevant preclinical model of Alzheimer's disease.

Identified in 1993, is the greatest genetic risk factor for sporadic Alzheimer's disease (AD), increasing risk up to 15-fold compared with , with decreasing AD risk. However, the functional effects of on AD pathology remain unclear and, in some cases, controversial. In vivo progress to understand how the human (h)- genotypes affect AD pathology has been limited by the lack of a tractable familial AD-transgenic (FAD-Tg) mouse model expressing h- rather than mouse (m)- The disparity between m- and h-apoE is relevant for virtually every AD-relevant pathway, including amyloid-β (Aβ) deposition and clearance, neuroinflammation, tau pathology, neural plasticity and cerebrovascular deficits.

Increased Plasma Beta-Secretase 1 May Predict Conversion to Alzheimer's Disease Dementia in Individuals With Mild Cognitive Impairment.

Background: Increased beta-secretase 1 (BACE1) activity has consistently been detected in brain tissue and cerebrospinal fluid of subjects with mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) compared with control subjects. The collection of cerebrospinal fluid by lumbar puncture is invasive. We sought to identify the presence of plasma BACE1 activity and determine potential alterations in subjects with MCI with clinical follow-up examinations for 3 years using patients with diagnosed probable AD dementia compared with healthy control subjects.

Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell.

The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting.

APOE ε4 specific imbalance of arachidonic acid and docosahexaenoic acid in serum phospholipids identifies individuals with preclinical Mild Cognitive Impairment/Alzheimer's Disease.

This study was designed to explore the influence of apolipoprotein E (APOE) on blood phospholipids (PL) in predicting preclinical Alzheimer's disease (AD). Lipidomic analyses were also performed on blood from an AD mouse model expressing human APOE isoforms (EFAD) and five AD mutations and from 195 cognitively normal participants, 23 of who converted to mild cognitive impairment (MCI)/AD within 3 years. APOE ε4-carriers converting to MCI/AD had high arachidonic acid (AA)/docosahexaenoic acid (DHA) ratios in PL compared to cognitively normal ε4 and non-ε4 carriers.

Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer's Disease.

Background: The APOE4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). It has been associated with an accumulation of amyloid-β (Aβ) in the brain, which is produced through the sequential cleavage of the amyloid-β precursor protein (AβPP) by β - and γ-secretases. Alternatively, AβPP is also cleaved by α -secretases such as A Disintegrin and Metalloproteinase Domain-containing Protein 10 (ADAM10).

Systematic Review of Genetic Risk Factors for Sustaining a Mild Traumatic Brain Injury.

This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury. We retrieved articles published in English from 1980 to July 2016 obtained from the online databases PubMed, PsycINFO, MEDLINE, Embase, and Web of Science. In total 5903 articles were identified, 77 underwent full-text screening, and 6 were included in this review.

Subfoveal Choroidal Thickness in Central Serous Chorioretinopathy: A Meta-Analysis.

Purpose: To evaluate the relationship between subfoveal choroidal thickness (SFCT) and eyes with central serous chorioretinopathy (CSC) versus fellow or control eyes.

Methods: We performed a meta-analysis using databases including PubMed, Embase and ISI Web of Science to find relevant studies. Weighted mean difference (WMD) was calculated for the SFCT in CSC eyes, the unaffected fellow eyes and normal controls.

Efferent influences on the bioelectrical activity of the retina in primates.

Purpose: The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established.

Sex chromosome abnormalities and psychiatric diseases.

Excesses of sex chromosome abnormalities in patients with psychiatric diseases have recently been observed. It remains unclear whether sex chromosome abnormalities are related to sex differences in some psychiatric diseases. While studies showed evidence of susceptibility loci over many sex chromosomal regions related to various mental diseases, others demonstrated that the sex chromosome aneuploidies may be the key to exploring the pathogenesis of psychiatric disease.

Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness.

Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI.

Acute or Delayed Treatment with Anatabine Improves Spatial Memory and Reduces Pathological Sequelae at Late Time-Points after Repetitive Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) has chronic and long-term consequences for which there are currently no approved pharmacological treatments. We have previously characterized the chronic neurobehavioral and pathological sequelae of a mouse model of repetitive mild TBI (r-mTBI) through to 2 years post-TBI. Despite the mild nature of the initial insult, secondary injury processes are initiated that involve neuroinflammatory and neurodegenerative pathways persisting and progressing for weeks and months post-injury and providing a potential window of opportunity for therapeutic intervention.

Auranofin Inhibits Retinal Pigment Epithelium Cell Survival through Reactive Oxygen Species-Dependent Epidermal Growth Factor Receptor/ Mitogen-Activated Protein Kinase Signaling Pathway.

Abnormal survival of retinal pigment epithelium (RPE) cells contributes to the pathogenesis of proliferative vitreoretinopathy (PVR), a sight-threatening disease. In this study, we explored the effect of the anti-rheumatic agent auranofin (AF) on RPE cell survival and studied the underlying signaling mechanisms in vitro. Our results showed that AF inhibited ARPE-19 cell survival in a dose and time-dependent manner.

Inflammatory changes in optic nerve after closed-head repeated traumatic brain injury: Preliminary study.

Background: Closed-head, repeated, mild traumatic brain injury (r-mTBI) leads to inflammatory and degenerative changes in the optic nerve of young wild type mice. This work has investigated whether similar changes may be present when the same model is applied to htau mice, a transgenic mouse in which the non-mutated human tau gene is expressed on a null murine tau background.

Methods: This study investigated neuropathological changes in the optic nerve in both young (15 weeks) and old (65-70 weeks) htau mice at 24 hours after r-mTBI or anaesthesia only (r-sham).

Chronic cerebrovascular abnormalities in a mouse model of repetitive mild traumatic brain injury.

Primary Objective: To investigate the status of the cerebrovasculature following repetitive mild traumatic brain injury (r-mTBI).

Research Design: TBI is a risk factor for development of various neurodegenerative disorders. A common feature of neurodegenerative disease is cerebrovascular dysfunction which includes alterations in cerebral blood flow (CBF).

Progression of tau pathology within cholinergic nucleus basalis neurons in chronic traumatic encephalopathy: A chronic effects of neurotrauma consortium study.

Objective: To test the hypothesis that the nucleus basalis of Meynert (nbM), a cholinergic basal forebrain (CBF) cortical projection system, develops neurofibrillary tangles (NFTs) during the progressive pathological stages of chronic traumatic encephalopathy (CTE) in the brain of athletes.

Method: To characterize NFT pathology, tau-antibodies marking early, intermediate and late stages of NFT development in CBF tissue obtained at autopsy from eighteen former athletes and veterans with a history of repetitive mild traumatic brain injury (TBI) were used.

Results: Analysis revealed that cholinergic nbM neurons develop intracellular tau-immunoreactive changes progressively across the pathological stages of CTE.

SUBTHRESHOLD MICROPULSE DIODE LASER VERSUS CONVENTIONAL LASER PHOTOCOAGULATION FOR DIABETIC MACULAR EDEMA: A Meta-Analysis of Randomized Controlled Trials.

Purpose: To evaluate the relative efficacy of subthreshold micropulse diode laser versus conventional laser photocoagulation for the treatment of diabetic macular edema.

Methods: A comprehensive literature search was conducted to find relevant randomized controlled trials (RCTs). Efficacy estimates were determined by comparing weighted mean differences of the mean change of best-corrected visual acuity and central macular thickness from baseline.

Why sex differences in schizophrenia?

Clinical observation shows that men and women are different in prevalence, symptoms, and responses to treatment of several psychiatric disorders, including schizophrenia. While the etiology of gender differences in schizophrenia is only partially understood, recent genetic studies suggest significant sex-specific pathways in the schizophrenia between men and women. More research is needed to understand the causal roles of sex differences in schizophrenia in order to ultimately develop sex-specific treatment of this serious mental illness.

Mild TBI Results in a Long-Term Decrease in Circulating Phospholipids in a Mouse Model of Injury.

Neurophysiological and neurological dysfunction is usually experienced for a short period of time in patients with mild traumatic brain injury (mTBI). However, around 15 % of patients exhibit symptoms months after TBI. Phospholipid (PL) changes have been observed in plasma from mTBI patients at chronic stages, suggesting a role in TBI pathology.

Inhibition of ADAM10 promotes the clearance of Aβ across the BBB by reducing LRP1 ectodomain shedding.

Background: Transport across the blood-brain barrier (BBB) is an important mediator of beta-amyloid (Aβ) accumulation in the brain and a contributing factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors responsible for the transport of Aβ in the BBB is the low density lipoprotein receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at the cell surface, which prevents endocytic transport of ligands.

European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow.

Introduction: In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers.

Genetics and Other Risk Factors for Past Concussions in Active-Duty Soldiers.

Risk factors for concussion in active-duty military service members are poorly understood. The present study examined the association between self-reported concussion history and genetics (apolipoprotein E [APOE], brain-derived neurotrophic factor [BDNF], and D2 dopamine receptor genes [DRD2]), trait personality measures (impulsive-sensation seeking and trait aggression-hostility), and current alcohol use. The sample included 458 soldiers who were preparing to deploy for Operation Iraqi Freedom/Operation Enduring Freedom.

Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.

Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals.

Brain-derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress.

Background: In addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment.

Methods: Both pre- and postdeployment data on 231 of 458 soldiers were analyzed.