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Brain, Behavior, and Immunity

Katie N Murray, Michelle E Edye, Maurizio Manca, Anthony C Vernon, Joanna M Oladipo, Victoria Fasolino, Michael K Harte, Varsha Mason, Ben Grayson, Patrick C McHugh, Irene Knuesel, Eric P Prinssen, Reinmar Hager, Joanna C Neill
Maternal immune activation (mIA) in rodents is rapidly emerging as a key model for neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. Here, we optimise a mIA model in rats, aiming to address certain limitations of current work in this area. Specifically, the lack of clear evidence for methodology chosen, identification of successful induction of mIA in the dams and investigation of male offspring only. We focus on gestational and early juvenile changes in offspring following mIA as detailed information on these critical early developmental time points is sparse...
September 12, 2018: Brain, Behavior, and Immunity
Claire-Marie Rangon, Anne-Laure Schang, Juliette Van Steenwinckel, Leslie Schwendimann, Sophie Lebon, Tingting Fu, Libo Chen, Veronique Beneton, Nathalie Journiac, Pierrette Young-Ten, Thomas Bourgeois, Johanna Maze, Boris Matrot, Ana A Baburamani, Veena Supramaniam, Carina Mallard, Lionel Trottet, A David Edwards, Henrik Hagberg, Bobbi Fleiss, Jingjun Li, Tsu Tshen Chuang, Pierre Gressens
Fifteen million babies are born preterm every year and a significant number suffer from permanent neurological injuries linked to white matter injury (WMI). A chief cause of preterm birth itself and predictor of the severity of WMI is exposure to maternal-fetal infection-inflammation such as chorioamnionitis. There are no neurotherapeutics for this WMI. To affect this healthcare need, the repurposing of drugs with efficacy in other white matter injury models is an attractive strategy. As such, we tested the efficacy of GSK247246, an H3R antagonist/inverse agonist, in a model of inflammation-mediated WMI of the preterm born infant recapitulating the main clinical hallmarks of human brain injury, which are oligodendrocyte maturation arrest, microglial reactivity, and hypomyelination...
September 12, 2018: Brain, Behavior, and Immunity
Sophia Kogan, Luz H Ospina, David Kimhy
Individuals with schizophrenia display substantial deficits in neurocognition, resulting in poor daily functioning and disability. Recent reports have suggested that neurocognitive dysfunction in this population is linked to increased inflammation. However, there is paucity of evidence supporting this link, as well as lack of information about the putative link of inflammation to daily functioning. We examined neurocognition (MCCB) and daily functioning (SLOF), as well as inflammatory markers (TNF-α, IL-6, IL-1β, and IL-12p70) in 41 individuals with schizophrenia...
September 12, 2018: Brain, Behavior, and Immunity
Andreza B Sonego, Douglas S Prado, Gabriel T Vale, Julia E Sepulveda-Diaz, Thiago M Cunha, Carlos R Tirapelli, Elaine A Del Bel, Rita Raisman-Vozari, Francisco S Guimarães
The chronic use of drugs that reduce the dopaminergic neurotransmission can cause a hyperkinetic movement disorder called tardive dyskinesia (TD). The pathophysiology of this disorder is not entirely understood but could involve oxidative and neuroinflammatory mechanisms. Cannabidiol (CBD), the major non-psychotomimetic compound present in Cannabis sativa plant, could be a possible therapeutic alternative for TD. This phytocannabinoid shows antioxidant, anti-inflammatory and antipsychotic properties and decreases the acute motor effects of classical antipsychotics...
September 11, 2018: Brain, Behavior, and Immunity
Jennifer E Graham-Engeland, Nancy L Sin, Joshua M Smyth, Dusti Jones, Erik L Knight, Martin J Sliwinski, David M Almeida, Mindy J Katz, Richard B Lipton, Christopher G Engeland
Very little research has assessed how measures of negative and positive affect (NA and PA) derived from assessments at multiple time points per day (e.g., via ecological momentary assessment [EMA]), as opposed to questionnaires that rely on recall over a longer period, are related to levels of peripheral inflammation. We examined how different indicators of NA and PA predicted concentrations of C-reactive protein (CRP) and seven peripheral inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8, IL-4, IL-10, and IFN-γ) that were examined in the form of an inflammatory composite...
September 11, 2018: Brain, Behavior, and Immunity
Canhua Xiao, Jonathan J Beitler, Kristin A Higgins, Evanthia C Wommack, Nabil F Saba, Dong M Shin, Deborah W Bruner, Andrew H Miller, Steve Cole
Previous studies have linked plasma inflammatory markers to elevated fatigue in patients with head and neck cancer (HNC). To identify the molecular mechanisms underlying this association, we conducted promoter-based bioinformatics analyses to determine the relationship between fatigue and specific gene expression profiles associated with inflammation in human papillomavirus (HPV)-related and -unrelated HNC patients undergoing treatment. Patients with newly diagnosed HNC without distant metastasis were assessed at baseline (pre-radiotherapy) and one-month post-radiotherapy...
September 11, 2018: Brain, Behavior, and Immunity
Julie Lasselin, Predrag Petrovic, Mats J Olsson, Sofie Paues-Göranson, Mats Lekander, Karin B Jensen, John Axelsson
BACKGROUND: People react very differently when sick, and there are only poor correlations between the intensity of the immune response and sickness behavior. Yet, alternative predictors of the individual differences in sickness are under-investigated. Based on the predictive coding model of placebo responses, where health outcomes are function of bottom-up sensory information and top-down expectancies, we hypothesized that individual differences in behavioral changes during sickness could be explained by individual top-down expectancies and prediction errors...
September 11, 2018: Brain, Behavior, and Immunity
Inken Waltl, Christopher Käufer, Ingo Gerhauser, Chintan Chhatbar, Luca Ghita, Ulrich Kalinke, Wolfgang Löscher
In the central nervous system (CNS), innate immune surveillance is mainly coordinated by microglia. These CNS resident myeloid cells are assumed to help orchestrate the immune response against infections of the brain. However, their specific role in this process and their interactions with CNS infiltrating immune cells, such as blood-borne monocytes and T cells are only incompletely understood. The recent development of PLX5622, a specific inhibitor of colony-stimulating factor 1 receptor that depletes microglia, allows studying the role of microglia in conditions of brain injury such as viral encephalitis, the most common form of brain infection...
September 11, 2018: Brain, Behavior, and Immunity
Cara M Hueston, James D O'Leary, Alan E Hoban, Danka A Kozareva, Lauren C Pawley, Olivia F O'Leary, John F Cryan, Yvonne M Nolan
Understanding the long-term consequences of chronic inflammation in the hippocampus may help to develop therapeutic targets for the treatment of cognitive disorders related to stress, ageing and neurodegeneration. The hippocampus is particularly vulnerable to increases in the pro-inflammatory cytokine interleukin-1β (IL-1β), a mediator of neuroinflammation, with elevated levels implicated in the aetiology of neurodegenerative diseases such as Alzheimer's and Parkinson's, and in stress-related disorders such as depression...
September 11, 2018: Brain, Behavior, and Immunity
Marina Dukhinova, Inna Kuznetsova, Ekaterina Kopeykina, Ekaterina Veniaminova, Amanda W Y Yung, Tatyana Veremeyko, Kseniia Levchuk, Natasha S Barteneva, Kenny Kam Wing Ho, Wing-Ho Yung, Julia Y H Liu, John Rudd, Sonata S Y Yau, Daniel C Anthony, Tatyana Strekalova, Eugene D Ponomarev
It is generally accepted that inflammation within the CNS contributes to neurodegeneration after traumatic brain injury (TBI), but it is not clear how inflammation is initiated in the absence of infection and whether this neuroinflammation is predominantly beneficial or detrimental. We have previously found that brain-enriched glycosphingolipids within neuronal lipid rafts (NLR) induced platelet degranulation and secretion of neurotransmitters and pro-inflammatory factors. In the present study, we compared TBI-induced inflammation and neurodegeneration in wild-type vs...
September 11, 2018: Brain, Behavior, and Immunity
M Sima Finy, Lisa M Christian
Women who have experienced significant adversities during childhood and adulthood are at risk for excessive inflammation during pregnancy, but the mechanisms are unclear. Using structural equation modeling, we examined pathways from childhood abuse history and current socioeconomic status (SES) to inflammatory markers through indicators of health risk, recent stressors, and psychological distress in 214 women assessed at mid-pregnancy (5-31 weeks gestation). Self-reported data on socioeconomic indicators, childhood trauma history, pre-pregnancy body mass index (BMI), smoking, sleep quality, interpersonal conflict, recent life events, perceived stress, and depressive symptoms were collected, and serum levels of C-reactive protein (CRP) and interleukin (IL)-6 were determined...
September 11, 2018: Brain, Behavior, and Immunity
Yanling Zhou, Wei Zheng, Weijian Liu, Chengyu Wang, Yanni Zhan, Hanqiu Li, Lijian Chen, Mingding Li, Yuping Ning
Ketamine has rapid antidepressant effects on treatment-resistant depression, but the biological mechanism underpinning this effect is less clear. Our aims were to examine whether kynurenine pathway metabolites were altered by six infusions of ketamine and whether these biological factors could act as potential biomarkers to predict ketamine's antidepressant effects. Six intravenous infusions of ketamine (0.5 mg/kg) were administered to 84 patients with unipolar and bipolar depression over a 12-d period. Symptom severity and response were assessed using the Montgomery-Asberg Scale (MADRS), and blood samples were collected at baseline and 24 hours following the first infusion and at 24 hours and 14 d after the sixth infusion (24 hours, 13 d and 26 d)...
September 10, 2018: Brain, Behavior, and Immunity
Didem Ağaç, Leonardo D Estrada, Robert Maples, Lora V Hooper, J David Farrar
The mammalian nervous system communicates important information about the environment to the immune system, but the underlying mechanisms are largely unknown. Secondary lymphoid organs are highly innervated by sympathetic neurons that secrete norepinephrine (NE) as the primary neurotransmitter. Immune cells express adrenergic receptors, enabling the sympathetic nervous system to directly control immune function. NE is a potent immunosuppressive factor and markedly inhibits TNF-α secretion from innate cells in response to lipopolysaccharide (LPS)...
September 5, 2018: Brain, Behavior, and Immunity
Luting Poh, Sung-Wook Kang, Sang-Ha Baik, Gavin Yong Quan Ng, David T She, Priyanka Balaganapathy, S Thameem Dheen, Tim Magnus, Mathias Gelderblom, Christopher G Sobey, Edward H Koo, David Y Fann, Thiruma V Arumugam
Stroke is the second leading cause of death in the world and a major cause of long-term disability. Recent evidence has provided insight into a newly described inflammatory mechanism that contributes to neuronal and glial cell death, and impaired neurological outcome following ischemic stroke - a form of sterile inflammation involving innate immune complexes termed inflammasomes. It has been established that inflammasome activation following ischemic stroke contributes to neuronal cell death, but little is known about inflammasome function and cell death in activated microglial cells following cerebral ischemia...
September 5, 2018: Brain, Behavior, and Immunity
Claudia Cristiano, Claudio Pirozzi, Lorena Coretti, Gina Cavaliere, Adriano Lama, Roberto Russo, Francesca Lembo, Maria Pina Mollica, Rosaria Meli, Antonio Calignano, Giuseppina Mattace Raso
Autism spectrum disorders (ASD) are a group of heterogeneous neurodevelopmental conditions characterized by impaired social interaction, and repetitive stereotyped behaviours. Interestingly, functional and inflammatory gastrointestinal diseases are often reported as a comorbidity in ASDs, indicating gut-brain axis as a novel emerging approach. Recently, a central role for peroxisome-proliferator activated receptor (PPAR)-α has been addressed in neurological functions, associated with the behaviour. Among endogenous lipids, palmitoylethanolamide (PEA), a PPAR-α agonist, has been extensively studied for its anti-inflammatory effects both at central and peripheral level...
September 5, 2018: Brain, Behavior, and Immunity
Xiao-Qian Li, Qian Yu, Wen-Fei Tan, Zai-Li Zhang, Hong Ma
BACKGROUND: Ischemia reperfusion (IR) injury affects neuronal function through multiple pathogeneses that induce neuroinflammation and cellular apoptosis. The important roles of microRNAs (miRs) in the regulation of spinal cord IR have been recently reported. Among these roles, we investigated whether miR-125b and its downstream targets regulated the p53 signalling network and participated in both inflammation and apoptosis. METHODS: An IR model was established via 12-min occlusion of the aortic arch...
September 5, 2018: Brain, Behavior, and Immunity
Divya Mehta, Joanne Voisey, Dagmar Bruenig, Wendy Harvey, Charles P Morris, Bruce Lawford, Ross McD Young
BACKGROUND: Posttraumatic stress disorder (PTSD) is a serious condition that emerges following trauma exposure and involves long-lasting psychological suffering and health-issues. Uncovering critical genes and molecular networks is essential to understanding the biology of the disorder. We performed a genome-wide scan to identify transcriptome signatures of PTSD. METHODS: Genome-wide peripheral blood transcriptomic data from 380 service personnel were investigated...
September 4, 2018: Brain, Behavior, and Immunity
Rachel M Graff, Hawley E Kunz, Nadia H Agha, Forrest L Baker, Mitzi Laughlin, Austin B Bigley, Melissa M Markofski, Emily C LaVoy, Emmanuel Katsanis, Richard A Bond, Catherine M Bollard, Richard J Simpson
Acute exercise preferentially mobilizes cytotoxic T-cells, NK-cells and non-classical monocytes to the bloodstream under the influence of hemodynamic forces and/or β2 -adrenergic receptor (β2 -AR) signaling. However, the relative contribution of these mechanisms to the redeployment of the most exercise-responsive cell types is largely unknown. We determined the lymphocyte and monocyte subtypes mobilized to blood during exercise via β2- AR signaling whilst controlling for β1- AR mediated reductions in hemodynamic forces...
August 30, 2018: Brain, Behavior, and Immunity
Michelle A Erickson, Joseph A Nicolazzo, William A Banks
This year's 2018 Named Series on blood-brain interfaces highlights the importance of brain barriers as mediators of neuroimmune communication and regulators of neurological function. The term "brain interfaces" reflects our growing understanding that brain barriers such as the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) are not only gatekeepers, but facilitators of bidirectional communication between the brain and periphery. There is also an emerging appreciation that CNS sites that are exposed to blood-borne immune molecules and cells, such as the leptomeninges and circumventricular organs, may also be considered brain interfaces with important homeostatic and pathological functions...
August 30, 2018: Brain, Behavior, and Immunity
Bruno B Lima, Muhammad Hammadah, Kobina Wilmot, Brad D Pearce, Amit Shah, Oleksiy Levantsevych, Belal Kaseer, Malik Obideen, Mohamad Mazen Gafeer, Jeong Hwang Kim, Samaah Sullivan, Tené T Lewis, Lei Weng, Lisa Elon, Lian Li, J Douglas Bremner, Paolo Raggi, Arshed Quyyumi, Viola Vaccarino
BACKGROUND: Posttraumatic Stress Disorder (PTSD) is prevalent among patients who survived an acute coronary syndrome, and is associated with adverse outcomes, but the mechanisms underlying these associations are unclear. Individuals with PTSD have enhanced sensitivity of the noradrenergic system to stress which may lead to immune activation. We hypothesized that survivors of a myocardial infarction (MI) who have PTSD would show an enhanced inflammatory response to acute psychological stress compared to those without PTSD...
August 30, 2018: Brain, Behavior, and Immunity
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