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Microglia function

Jessica C Stark, Euan Wallace, Rebecca Lim, Bryan Leaw
Microglia, the resident immune cells in the brain, are the first responders to inflammation or injury in the central nervous system. Recent research has revealed microglia to be dynamic, capable of assuming both pro-inflammatory and anti-inflammatory phenotypes. Both M1 (pro-inflammatory) and M2 (pro-reparative) phenotypes play an important role in neuroinflammatory conditions such as perinatal brain injury, and exhibit differing functions in response to certain environmental stimuli. The modulation of microglial activation has been noted to confer neuroprotection thus suggesting microglia may have therapeutic potential in brain injury...
February 16, 2018: Journal of Visualized Experiments: JoVE
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Yuko Saito
Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of either triggering receptor expressed on myeloid cells 2 ( TREM2 ) or TYRO protein tyrosine kinase binding protein ( TYROBP ), alternatively named DNAX-activation protein 12 ( DAP12 ), both of which are expressed on microglia in the brain and form the receptor-adaptor complex that chiefly recognizes anionic lipids. TREM2 transmits the signals involved in microglial survival, proliferation, chemotaxis, and phagocytosis...
February 2018: Intractable & Rare Diseases Research
Caroline André, Caterina Catania, Julie Remus-Borel, Elodie Ladeveze, Thierry Leste-Lasserre, Wilfrid Mazier, Elke Binder, Delphine Gonzales, Samantha Clark, Omar Guzman-Quevedo, Djoher Nora Abrous, Sophie Layé, Daniela Cota
Ciliary neurotrophic factor (CNTF) potently decreases food intake and body weight in diet-induced obese mice by acting through neuronal circuits and pathways located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts pro-inflammatory actions within the brain. Here we tested whether CNTF modifies energy balance by inducing inflammatory responses in the ARC and whether these effects depend upon the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates both energy metabolism and inflammation...
March 13, 2018: Brain, Behavior, and Immunity
Moumita Datta, Ori Staszewski, Elena Raschi, Maximilian Frosch, Nora Hagemeyer, Tuan Leng Tay, Thomas Blank, Mario Kreutzfeldt, Doron Merkler, Stephanie Ziegler-Waldkirch, Patrick Matthias, Melanie Meyer-Luehmann, Marco Prinz
Microglia as tissue macrophages contribute to the defense and maintenance of central nervous system (CNS) homeostasis. Little is known about the epigenetic signals controlling microglia function in vivo. We employed constitutive and inducible mutagenesis in microglia to delete two class I histone deacetylases, Hdac1 and Hdac2. Prenatal ablation of Hdac1 and Hdac2 impaired microglial development. Mechanistically, the promoters of pro-apoptotic and cell cycle genes were hyperacetylated in absence of Hdac1 and Hdac2, leading to increased apoptosis and reduced survival...
March 7, 2018: Immunity
Hongbei Xu, Wenyi Qin, Xiao Hu, Song Mu, Jun Zhu, Wenhao Lu, Yong Luo
BACKGROUND: Ischemic stroke-induced neuroinflammation is mainly mediated by microglial cells. The nuclear factor kappa B (NF-κB) pathway is the key transcriptional pathway that initiates inflammatory responses following cerebral ischemia. OTULIN, a critical negative regulator of the NF-κΒ signaling pathway, exerts robust effects on peripheral immune cell-mediated inflammation and is regarded as an essential mediator for repressing inflammation in vivo. The effect of OTULIN on inflammatory responses in the central nervous system (CNS) was previously unstudied...
March 15, 2018: Journal of Neuroinflammation
Augusta Pisanu, Laura Boi, Giovanna Mulas, Saturnino Spiga, Sandro Fenu, Anna R Carta
Neuroinflammation is a main component of Parkinson's disease (PD) neuropathology, where unremitting reactive microglia and microglia-secreted soluble molecules such as cytokines, contribute to the neurodegenerative process as part of an aberrant immune reaction. Besides, pro-inflammatory cytokines, predominantly TNF-α, play an important neuromodulatory role in the healthy and diseased brain, being involved in neurotransmitter metabolism, synaptic scaling and brain plasticity. Recent preclinical studies have evidenced an exacerbated neuroinflammatory reaction in the striatum of parkinsonian rats that developed dyskinetic responses following L-DOPA administration...
March 14, 2018: Journal of Neural Transmission
Changguo Ma, Chunjie Gu, Yongxia Huo, Xiaoyan Li, Xiong-Jian Luo
Genome-wide association studies (GWAS) have identified more than 100 loci that show robust association with schizophrenia risk. However, due to the complexity of linkage disequilibrium and gene regulatory, it is challenging to pinpoint the causal genes at the risk loci and translate the genetic findings from GWAS into disease mechanism and clinical treatment. Here we systematically predicted the plausible candidate causal genes for schizophrenia at genome-wide level. We utilized different approaches and strategies to predict causal genes for schizophrenia, including Sherlock, SMR, DAPPLE, Prix Fixe, NetWAS, and DEPICT...
March 15, 2018: Translational Psychiatry
Vipan K Parihar, Mattia Maroso, Amber Syage, Barrett D Allen, Maria C Angulo, Ivan Soltesz, Charles L Limoli
Of the many perils associated with deep space travel to Mars, neurocognitive complications associated with cosmic radiation exposure are of particular concern. Despite these realizations, whether and how realistic doses of cosmic radiation cause cognitive deficits and neuronal circuitry alterations several months after exposure remains unclear. In addition, even less is known about the temporal progression of cosmic radiation-induced changes transpiring over the duration of a time period commensurate with a flight to Mars...
March 11, 2018: Experimental Neurology
Jun Ding, James S Hagood, Namasivayam Ambalavanan, Naftali Kaminski, Ziv Bar-Joseph
The Dynamic Regulatory Events Miner (DREM) software reconstructs dynamic regulatory networks by integrating static protein-DNA interaction data with time series gene expression data. In recent years, several additional types of high-throughput time series data have been profiled when studying biological processes including time series miRNA expression, proteomics, epigenomics and single cell RNA-Seq. Combining all available time series and static datasets in a unified model remains an important challenge and goal...
March 14, 2018: PLoS Computational Biology
Alison M Earley, Cameron T Dixon, Celia E Shiau
FOXQ1 is a member of the forkhead-box transcription factor family that has important functions in development, cancer, aging, and many cellular processes. The role of FOXQ1 in cancer biology has raised intense interest, yet much remains poorly understood. We investigated the possible function of the two zebrafish orthologs (foxq1a and foxq1b) of human FOXQ1 in innate immune cell development and function. We employed CRISPR-Cas9 targeted mutagenesis to create null mutations of foxq1a and foxq1b in zebrafish...
2018: PloS One
Santa Mammana, Paolo Fagone, Eugenio Cavalli, Maria Sofia Basile, Maria Cristina Petralia, Ferdinando Nicoletti, Placido Bramanti, Emanuela Mazzon
In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, as the former derive from yolk sac erythromyeloid precursors and the latter from the fetal liver or bone marrow. Accordingly, specific phenotypic patterns characterize each population...
March 13, 2018: International Journal of Molecular Sciences
Peter M Grace, Xiaohui Wang, Keith A Strand, Michael V Baratta, Yingning Zhang, Erika L Galer, Hang Yin, Steven F Maier, Linda R Watkins
The absence of selective pharmacological tools is a major barrier to the in vivo study of microglia. To address this issue, we developed a Gq - and Gi -coupled Designer Receptor Exclusively Activated by a Designer Drug (DREADD) to enable selective stimulation or inhibition of microglia, respectively. DREADDs under a CD68 (microglia/macrophage) promoter were intrathecally transfected via an AAV9 vector. Naïve male rats intrathecally transfected with Gq (stimulatory) DREADDs exhibited significant allodynia following intrathecal administration of the DREADD-selective ligand clozapine-N-oxide (CNO), which was abolished by intrathecal interleukin-1 receptor antagonist...
March 9, 2018: Experimental Neurology
Riccardo Natoli, Nilisha Fernando, Tess Dahlenburg, Haihan Jiao, Riemke Aggio-Bruce, Nigel L Barnett, Juan Manuel Chao de la Barca, Guillaume Tcherkez, Pascal Reynier, Johnny Fang, Joshua A Chu-Tan, Krisztina Valter, Jan Provis, Matt Rutar
Purpose: Systemic increases in reactive oxygen species, and their association with inflammation, have been proposed as an underlying mechanism linking obesity and age-related macular degeneration (AMD). Studies have found increased levels of oxidative stress biomarkers and inflammatory cytokines in obese individuals; however, the correlation between obesity and retinal inflammation has yet to be assessed. We used the leptin-deficient (ob/ob) mouse to further our understanding of the contribution of obesity to retinal oxidative stress and inflammation...
2018: Molecular Vision
Laura K Fonken, Matthew G Frank, Andrew D Gaudet, Heather M D'Angelo, Rachel A Daut, Emma C Hampson, Monica T Ayala, Linda R Watkins, Steven F Maier
Exposure to stressors can enhance neuroinflammatory responses, and both stress and neuroinflammation are predisposing factors in the development of psychiatric disorders. Females suffer disproportionately more from several psychiatric disorders, yet stress-induced changes in neuroinflammation have primarily been studied in males. Here we tested whether exposure to inescapable tail shock sensitizes or 'primes' neuroinflammatory responses in male and female rats. At 24 h post-stress, male and female rats exposed to a peripheral immune challenge enhanced neuroinflammatory responses and exacerbated anxiety- and depressive-like behaviors...
March 7, 2018: Brain, Behavior, and Immunity
Jacki L Coburn, Toby B Cole, Khoi T Dao, Lucio G Costa
Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice...
March 10, 2018: Archives of Toxicology
Carlos R Dostal, Megan Carson Sulzer, Keith W Kelley, Gregory G Freund, Robert H McCusker
Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the Kynurenine Pathway which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2). Although implicated as mediating changes in behavior, detecting stress-induced DO expression has proven inconsistent...
December 2017: Neurobiology of Stress
Nicole Rosskothen-Kuhl, Heika Hildebrandt, Ralf Birkenhäger, Robert-Benjamin Illing
Neuron-glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adulthood, both groups received an intracochlear electrode into the left cochlea and were continuously stimulated for 1 or 7 days after waking up from anesthesia. Normal hearing and deafness were assessed by auditory brainstem responses (ABRs)...
2018: Frontiers in Cellular Neuroscience
Marta Machado-Pereira, Tiago Santos, Lino Ferreira, Liliana Bernardino, Raquel Ferreira
Perinatal stroke is often difficult to diagnose and an established treatment has not yet been validated, except for symptomatic measures. Herein, we propose to test the neuroprotective potential of the intravenous injection of retinoic acid-loaded nanoparticles (RA-NP) upon ischemic injury to the immature brain. The role of RA-NP on endothelial cells and organotypic slice cultures exposed to oxygen and glucose deprivation was assessed by evaluating markers pertaining to survival, proliferation, oxidative stress (NO, ROS), neuronal damage (enolase), vascular oxidation (p47phox) and microglia activation (CD68)...
March 5, 2018: Neuroscience Letters
Saurabh Dhanda, Smriti Gupta, Avishek Halder, Aditya Sunkaria, Rajat Sandhir
Chronic liver disease per se induces neuroinflammation that contributes to cognitive deficits in hepatic encephalopathy (HE). However, the processes by which pro-inflammatory molecules result in cognitive impairment still remain unclear. In the present study, a significant increase in the activity of liver function enzymes viz. alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) was observed along with increase in plasma ammonia levels after four weeks of bile duct ligation (BDL) in rats suggesting hepatocellular damage...
March 5, 2018: Brain, Behavior, and Immunity
Kaitryn E Ronning, Gabriel Peinado Allina, Eric B Miller, Robert J Zawadzki, Edward N Pugh, Rolf Hermann, Marie E Burns
Rods and cones mediate visual perception over 9 log units of light intensities, with both photoreceptor types contributing to a middle 3-log unit range that comprises most night-time conditions. Rod function in this mesopic range has been difficult to isolate and study in vivo because of the paucity of mutants that abolish cone signaling without causing photoreceptor degeneration. Here we describe a novel Gnat2 knockout mouse line (Gnat2-/- ) ideal for dissecting rod and cone function. In this line, loss of Gnat2 expression abolished cone phototransduction, yet there was no loss of cones, disruption of the photoreceptor mosaic, nor change in general retinal morphology up to at least 9 months of age...
March 5, 2018: Experimental Eye Research
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