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Glutamatergic dysregulation

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https://www.readbyqxmd.com/read/29315577/bidirectional-variation-in-glutamate-efflux-in-the-medial-prefrontal-cortex-induced-by-selective-positive-and-negative-allosteric-mglur5-modulators
#1
Sarah N Isherwood, Trevor W Robbins, Jeffrey W Dalley, Anton Pekcec
Dysregulation of prefrontal cortical glutamatergic signalling via NMDA receptor hypofunction has been implicated in cognitive dysfunction and impaired inhibitory control in such neuropsychiatric disorders as schizophrenia, attention deficit hyperactivity disorder and drug addiction. Although NMDA receptors functionally interact with metabotropic glutamate receptor 5 (mGluR5), the consequence of this interaction for glutamate release in the prefrontal cortex (PFC) is unknown. We therefore investigated the effects of positive and negative allosteric mGluR5 modulation on changes in extracellular glutamate efflux in the medial PFC (mPFC) induced by systemic administration of the non-competitive NMDA receptor antagonist dizocilpine (or MK801) in rats...
January 6, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29311593/neogenin-a-regulator-of-adult-hippocampal-neurogenesis-prevents-depressive-like-behavior
#2
Dong Sun, Xiang-Dong Sun, Lu Zhao, Dae-Hoon Lee, Jin-Xia Hu, Fu-Lei Tang, Jin-Xiu Pan, Lin Mei, Xiao-Juan Zhu, Wen-Cheng Xiong
Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation...
January 8, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29259026/early-vglut1-specific-parallel-fiber-synaptic-deficits-and-dysregulated-cerebellar-circuit-in-the-kiko-mouse-model-of-friedreich-ataxia
#3
Hong Lin, Jordi Magrane, Elisia M Clark, Sarah M Halawani, Nathan Warren, Amy Rattelle, David R Lynch
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder with progressive ataxia that affects both the peripheral and central nervous system (CNS). While later CNS neuropathology involves loss of large principal neurons and glutamatergic and GABAergic synaptic terminals in the cerebellar dentate nucleus, early pathological changes in FRDA cerebellum remain largely uncharacterized. Here, we report early cerebellar VGLUT1 (SLC17A7)-specific parallel fiber (PF) synaptic deficits and dysregulated cerebellar circuit in the frataxin knock-in/knockout (KIKO) FRDA mouse model...
December 19, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29177809/parallel-in-vivo-and-in-vitro-transcriptomics-analysis-reveals-calcium-and-zinc-signalling-in-the-brain-as-sensitive-targets-of-hbcd-neurotoxicity
#4
V Reffatto, J D Rasinger, T S Carroll, T Ganay, A-K Lundebye, I Sekler, M Hershfinkel, C Hogstrand
Hexabromocyclododecane (HBCD) is a brominated flame retardant (BFR) that accumulates in humans and affects the nervous system. To elucidate the mechanisms of HBCD neurotoxicity, we used transcriptomic profiling in brains of female mice exposed through their diet to HBCD (199 mg/kg body weight per day) for 28 days and compared with those of neuronal N2A and NSC-19 cell lines exposed to 1 or 2 µM HBCD. Similar pathways and functions were affected both in vivo and in vitro, including Ca2+ and Zn2+ signalling, glutamatergic neuron activity, apoptosis, and oxidative stress...
November 25, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29121220/pathway-specific-control-of-striatal-neuron-vulnerability-by-corticostriatal-cannabinoid-cb1-receptors
#5
Andrea Ruiz-Calvo, Irene B Maroto, Raquel Bajo-Grañeras, Anna Chiarlone, Ángel Gaudioso, José J Ferrero, Eva Resel, José Sánchez-Prieto, José A Rodríguez-Navarro, Giovanni Marsicano, Ismael Galve-Roperh, Luigi Bellocchio, Manuel Guzmán
The vast majority of neurons within the striatum are GABAergic medium spiny neurons (MSNs), which receive glutamatergic input from the cortex and thalamus, and form two major efferent pathways: the direct pathway, expressing dopamine D1 receptor (D1R-MSNs), and the indirect pathway, expressing dopamine D2 receptor (D2R-MSNs). While molecular mechanisms of MSN degeneration have been identified in animal models of striatal damage, the molecular factors that dictate a selective vulnerability of D1R-MSNs or D2R-MSNs remain unknown...
October 31, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29104034/distribution-of-the-branched-chain-%C3%AE-ketoacid-dehydrogenase-complex-e1%C3%AE-subunit-and-glutamate-dehydrogenase-in-the-human-brain-and-their-role-in-neuro-metabolism
#6
Jonathon Hull, Marcela Usmari Moraes, Emma Brookes, Seth Love, Myra E Conway
Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branched-chain amino acids (BCAAs) acting as key nitrogen donors for de novo glutamate synthesis. Despite the importance of these major metabolites, their metabolic pathway in the human brain is still not well characterised. The metabolic pathways that influence the metabolism of BCAAs have been well characterised in rat models. However, the expression of key proteins such as the branched-chain α-ketoacid dehydrogenase (BCKD) complex and glutamate dehydrogenase isozymes (GDH) in the human brain is still not well characterised...
November 9, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29097598/fgf-fgfr-mediates-the-activity-dependent-dendritogenesis-of-layer-iv-neurons-during-barrel-formation
#7
Jui-Yen Huang, Marisha Lynn Miskus, Hui-Chen Lu
Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) are known for their potent effects on cell proliferation/differentiation and cortical patterning in the developing brain. However, little is known regarding FGFs/FGFRs' roles in cortical circuit formation. Here we show that Fgfr1/2/3 and Fgf7/9/10/22 mRNAs are expressed in the developing primary somatosensory (S1) barrel cortex. Barrel cortex layer IV spiny stellate cells (bSCs) are the primary recipients of ascending sensory information via thalamocortical axons (TCAs)...
November 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29091022/evolution-of-circuits-regulating-pleasure-and-happiness-with-the-habenula-in-control
#8
Anton J M Loonen, Svetlana A Ivanova
The habenula, which in humans is a small nuclear complex within the epithalamus, plays an essential role in regulating the intensity of reward-seeking and adversity-avoiding behavior in all vertebrate ancestors by regulating the activity of ascending midbrain monoaminergic tracts. In lampreys, considered to possess a brain comparable to humans' earliest evolutionary vertebrate ancestor, the activity of the lateral habenula is controlled by a subset of glutamatergic neurons of the animal's pallidum (habenula-projecting globus pallidus) that inhibit reward-seeking behavior when this conduct is not successful enough...
November 1, 2017: CNS Spectrums
https://www.readbyqxmd.com/read/29024713/a-lack-of-glun2a-containing-nmda-receptors-confers-a-vulnerability-to-redox-dysregulation-consequences-on-parvalbumin-interneurons-and-their-perineuronal-nets
#9
Romain Cardis, Jan-Harry Cabungcal, Daniella Dwir, Kim Q Do, Pascal Steullet
The GluN2A subunit of NMDA receptors (NMDARs) plays a critical role during postnatal brain development as its expression increases while Glun2B expression decreases. Mutations and polymorphisms in GRIN2A gene, coding for GluN2A, are linked to developmental brain disorders such as mental retardation, epilepsy, schizophrenia. Published data suggest that GluN2A is involved in maturation and phenotypic maintenance of parvalbumin interneurons (PVIs), and these interneurons suffer from a deficient glutamatergic neurotransmission via GluN2A-containing NMDARs in schizophrenia...
October 10, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28967533/disruption-of-conscious-access-in-schizophrenia
#10
REVIEW
Lucie Berkovitch, Stanislas Dehaene, Raphaël Gaillard
Schizophrenia is a severe and complex psychiatric disorder resulting in delusions, hallucinations, and cognitive impairments. Across a variety of paradigms, an elevated threshold for conscious perception has been repeatedly observed in persons with schizophrenia. Remarkably, even subtle measures of subliminal processing appear to be preserved. We argue here that the dissociation between impaired conscious access and intact unconscious processing may be due to a specific disruption of top-down attentional amplification...
November 2017: Trends in Cognitive Sciences
https://www.readbyqxmd.com/read/28940879/phosphorylation-of-calcium-calmodulin-dependent-protein-kinase-ii-in-the-rat-dorsal-medial-prefrontal-cortex-is-associated-with-alcohol-induced-cognitive-inflexibility
#11
Luis A Natividad, Michael Q Steinman, Sarah A Laredo, Cristina Irimia, Ilham Y Polis, Robert Lintz, Matthew W Buczynski, Rémi Martin-Fardon, Marisa Roberto, Loren H Parsons
Repeated cycles of alcohol [ethanol (EtOH)] intoxication and withdrawal dysregulate excitatory glutamatergic systems in the brain and induce neuroadaptations in the medial prefrontal cortex (mPFC) that contribute to cognitive dysfunction. The mPFC is composed of subdivisions that are functionally distinct, with dorsal regions facilitating drug-cue associations and ventral regions modulating new learning in the absence of drug. A key modulator of glutamatergic activity is the holoenzyme calcium/calmodulin-dependent protein kinase II (CaMKII) that phosphorylates ionotropic glutamate receptors...
September 22, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28932183/plant-polyphenols-and-exendin-4-prevent-hyperactivity-and-tnf-%C3%AE-release-in-lps-treated-in-vitro-neuron-astrocyte-microglial-networks
#12
Francesca Gullo, Michela Ceriani, Alessia D'Aloia, Enzo Wanke, Andrew Constanti, Barbara Costa, Marzia Lecchi
Increasing evidence supports a decisive role for neuroinflammation in the neurodegenerative process of several central nervous system (CNS) disorders. Microglia are essential mediators of neuroinflammation and can regulate a broad spectrum of cellular responses by releasing reactive oxygen intermediates, nitric oxide, proteases, excitatory amino acids, and cytokines. We have recently shown that also in ex-vivo cortical networks of neurons, astrocytes and microglia, an increased level of tumor necrosis factor-alpha (TNF-α) was detected a few hours after exposure to the bacterial endotoxin lipopolysaccharide (LPS)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28928363/an-autism-spectrum-disorder-related-de-novo-mutation-hotspot-discovered-in-the-gef1-domain-of-trio
#13
Anastasiia Sadybekov, Chen Tian, Cosimo Arnesano, Vsevolod Katritch, Bruce E Herring
The Rho guanine nucleotide exchange factor (RhoGEF) Trio promotes actin polymerization by directly activating the small GTPase Rac1. Recent studies suggest that autism spectrum disorder (ASD)-related behavioral phenotypes in animal models of ASD can be produced by dysregulation of Rac1's control of actin polymerization at glutamatergic synapses. Here, in humans, we discover a large cluster of ASD-related de novo mutations in Trio's Rac1 activating domain, GEF1. Our study reveals that these mutations produce either hypofunctional or hyperfunctional forms of Trio in rodent neurons in vitro...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28924227/implication-of-the-glutamate-cystine-antiporter-xct-in-schizophrenia-cases-linked-to-impaired-gsh-synthesis
#14
M Fournier, A Monin, C Ferrari, P S Baumann, P Conus, K Do
xCT is the specific chain of the cystine/glutamate antiporter, which is widely reported to support anti-oxidant defenses in vivo. xCT is therefore at the crossroads between two processes that are involved in schizophrenia: oxidative stress and glutamatergic neurotransmission. But data from human studies implicating xCT in the illness and clarifying the upstream mechanisms of xCT imbalance are still scarce. Low glutathione (GSH) levels and genetic risk in GCLC (Glutamate-Cysteine Ligase Catalytic subunit), the gene of limiting synthesizing enzyme for GSH, are both associated with schizophrenia...
September 18, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28820053/neurobiological-mechanisms-of-stress-resilience-and-implications-for-the-aged-population
#15
Charlène Faye, Josephine C Mcgowan, Christine A Denny, Denis J David
Stress is a common reaction to an environmental adversity, but a dysregulation of the stress response can lead to psychiatric illnesses such as major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and anxiety disorders. Yet, not all individuals exposed to stress will develop psychiatric disorders; those with enhanced stress resilience mechanisms have the ability to adapt successfully to stress without developing persistent psychopathology. Notably, the potential to enhance stress resilience in at-risk populations may prevent the onset of stress-induced psychiatric disorders...
August 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28800512/metabotropic-glutamate-receptors-as-emerging-research-targets-in-bipolar-disorder
#16
REVIEW
Caren J Blacker, Charles P Lewis, Mark A Frye, Marin Veldic
Glutamatergic dysregulation is implicated in the neuropathology of bipolar disorder (BD). There is increasing interest in investigating the role of metabotropic glutamate receptors (mGluRs) in BD and as a target for treatment intervention. Bipolar mGluR studies (published January 1992-April 2016) were identified via PubMed, Embase, Web of Science, and Scopus. Full-text screening, data extraction, and quality appraisal were conducted in duplicate, with strict inclusion and exclusion criteria. The initial literature search for mGluRs in BD, including non-bipolar mood disorders and primary psychotic disorders, identified 1544 articles...
November 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28796815/effect-of-teriflunomide-on-cortex-basal-ganglia-thalamus-cxbgth-circuit-glutamatergic-dysregulation-in-the-theiler-s-murine-encephalomyelitis-virus-mouse-model-of-multiple-sclerosis
#17
Claire M Modica, Ferdinand Schweser, Michelle L Sudyn, Nicola Bertolino, Marilena Preda, Paul Polak, Danielle M Siebert, Jacqueline C Krawiecki, Michele Sveinsson, Jesper Hagemeier, Michael G Dwyer, Suyog Pol, Robert Zivadinov
BACKGROUND: Pathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors. OBJECTIVES: To investigate the effect of an immunomodulatory therapy (teriflunomide, Aubagio®) on changes of the CxBGTh loop in the Theiler's Murine Encephalomyelitis Virus, (TMEV) mouse model of MS...
2017: PloS One
https://www.readbyqxmd.com/read/28738353/inflammation-effects-on-glutamate-as-a-pathway-to-neuroprogression-in-mood-disorders
#18
Ebrahim Haroon, Andrew H Miller
Neuroprogression is a term used to describe worsening psychopathology, poor treatment response, and declining cognitive and functional outcomes among patients with chronic mental disorders. Chronic inflammatory activation and glutamate-mediated excitotoxicity are two key etiological factors implicated in the development of neuroprogression. In this chapter, we hypothesize that the association between chronic inflammatory activation, neuroprogression, and glutamate dysregulation might be mediated by glial dysfunction...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28709906/effects-of-feeding-time-on-daily-rhythms-of-neuropeptide-and-clock-gene-expression-in-the-rat-hypothalamus
#19
Dawei Wang, Anne-Loes Opperhuizen, Jane Reznick, Nigel Turner, Yan Su, Gregory J Cooney, Andries Kalsbeek
Shiftworkers are exposed to several adverse health conditions, one being eating at night. Food consumption at an unnatural time-of-day is thought to be one of the main factors responsible for the increased risk of developing metabolic diseases, such as obesity and diabetes mellitus. The underlying mechanism is considered to include disruption of the circadian organization of physiology, leading to disruption of metabolism. When food is consumed at night, the hypothalamus, a brain region central to homeostasis, receives contradicting input from the central clock and the systemic circulation...
July 11, 2017: Brain Research
https://www.readbyqxmd.com/read/28683776/trpa1-channels-promote-astrocytic-ca-2-hyperactivity-and-synaptic-dysfunction-mediated-by-oligomeric-forms-of-amyloid-%C3%AE-peptide
#20
Anthony Bosson, Adrien Paumier, Sylvie Boisseau, Muriel Jacquier-Sarlin, Alain Buisson, Mireille Albrieux
BACKGROUND: Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease (AD). However, the key mechanisms that maintain plasticity of synapses during adulthood or initiate synapse dysfunction in AD remain unknown. Recent studies suggest that astrocytes contribute to functional changes observed during synaptic plasticity and play a major role in synaptic dysfunction but astrocytes behavior and involvement in early phases of AD remained largely undefined. METHODS: We measure astrocytic calcium activity in mouse CA1 hippocampus stratum radiatum in both the global astrocytic population and at a single cell level, focusing in the highly compartmentalized astrocytic arbor...
July 6, 2017: Molecular Neurodegeneration
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