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https://www.readbyqxmd.com/read/29143330/short-term-high-fat-diet-primes-excitatory-synapses-for-long-term-depression-in-orexin-neurons
#1
Victoria Linehan, Lisa Fang, Michiru Hirasawa
Overconsumption of high-fat diets is one of the strongest contributing factors to the rise of obesity rates. Orexin neurons are known to be activated by palatable high-fat diet and mediate the activation of the mesolimbic reward pathway, resulting in further food intake. While short-term exposure to high-fat diet is known to induce synaptic plasticity within the mesolimbic pathway, it is unknown if such changes occur in orexin neurons. To investigate this, 3-week old male rats were fed a palatable high-fat western diet (WD) or control chow for 1 week and then in vitro patch clamp recording was performed...
November 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29100629/metabotropic-glutamatergic-receptor-5-and-stress-disorders-knowledge-gained-from-receptor-imaging-studies
#2
REVIEW
Irina Esterlis, Sophie E Holmes, Priya Sharma, John H Krystal, Christine DeLorenzo
The metabotropic glutamatergic receptor subtype 5 (mGluR5) may represent a promising therapeutic target for stress-related psychiatric disorders. Here, we describe mGluR5 findings in stress disorders, particularly major depressive disorder (MDD), highlighting insights from positron emission tomography studies. Positron emission tomography studies report either no differences or lower mGluR5 in MDD, potentially reflecting MDD heterogeneity. Unlike the rapidly acting glutamatergic agent ketamine, mGluR5-specific modulation has not yet shown antidepressant efficacy in MDD and bipolar disorder...
September 19, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29074619/presynaptic-mglur5-receptor-controls-glutamatergic-input-through-protein-kinase-c-nmda-receptors-in-paclitaxel-induced-neuropathic-pain
#3
Jing-Dun Xie, Shao-Rui Chen, Hui-Lin Pan
Chemotherapeutic drugs such as paclitaxel cause painful peripheral neuropathy in many cancer patients and survivors. Although NMDA receptors (NMDARs) at primary afferent terminals are known to be critically involved in chemotherapy-induced chronic pain, the upstream signaling mechanism that leads to presynaptic NMDAR activation is unclear. Group I metabotropic glutamate receptors (mGluRs) play a role in synaptic plasticity and NMDAR regulation. Here we report that the Group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of monosynaptic EPSCs evoked from the dorsal root...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29070854/altered-norbin-expression-in-patients-with-epilepsy-and-a-rat-model
#4
Yali Xu, Zengyou Li, Li Yao, Xingping Zhang, Dan Gan, Manchun Jiang, Na Wang, Guojun Chen, Xuefeng Wang
Norbin is widely distributed in neuronal tissues, is a regulator of Ca2(+)/calmodulin-dependent protein kinase II (CaMKII) phosphorylation. Norbin is also an important endogenous modulator of metabotropic glutamate receptor 5 (mGluR5) signaling, and nervous system-specific homozygous gene disruptions, result in epileptic seizures. In this study, we aimed to investigate norbin expression patterns in epilepsy and to elucidate the relationships between norbin and mGluR5 and p-CaMKII in epilepsy. Double-immunolabeling, immunohistochemistry and immunoblotting studies showed that norbin was downregulated in the temporal neocortex of patients with temporal lobe epilepsy (TLE) compared with control subjects...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29062097/altered-surface-mglur5-dynamics-provoke-synaptic-nmdar-dysfunction-and-cognitive-defects-in-fmr1-knockout-mice
#5
Elisabetta Aloisi, Katy Le Corf, Julien Dupuis, Pei Zhang, Melanie Ginger, Virginie Labrousse, Michela Spatuzza, Matthias Georg Haberl, Lara Costa, Ryuichi Shigemoto, Anke Tappe-Theodor, Filippo Drago, Pier Vincenzo Piazza, Christophe Mulle, Laurent Groc, Lucia Ciranna, Maria Vincenza Catania, Andreas Frick
Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub-cellular level, and related synaptic and cognitive phenotypes are unexplored. Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5 cell-surface mobility, synaptic N-methyl-D-aspartate receptor (NMDAR) function, and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse. Using single-molecule tracking, we found that mGluR5 was significantly more mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic surface co-clustering of mGluR5 and NMDAR...
October 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29055799/altered-mglur5-binding-potential-and-glutamine-concentration-in-the-6-ohda-rat-model-of-acute-parkinson-s-disease-and-levodopa-induced-dyskinesia
#6
Melissa Crabbé, Anke Van der Perren, Akila Weerasekera, Uwe Himmelreich, Veerle Baekelandt, Koen Van Laere, Cindy Casteels
Several lines of evidence point to alterations in glutamatergic signaling in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), involving the metabotropic glutamate receptor type 5 (mGluR5). Using small-animal positron emission tomography (PET) with [(18)F]FPEB and proton magnetic resonance spectroscopy, we investigated cerebral changes in the mGluR5 and glutamate/glutamine availability in vivo in PD rats and following onset of LIDs. In parallel, behavioral tests were performed. Comparing PD to control rats, mGluR5 binding potential was decreased in a cluster comprising the bilateral caudate-putamen (CP), ipsilateral motor cortex and somatosensory cortex, and the contralateral somatosensory cortex and parietal association cortex, with the most pronounced reduction in the ipsilateral CP...
September 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29051582/a-role-for-the-purinergic-receptor-p2x3-in-astrocytes-in-the-mechanism-of-craniofacial-neuropathic-pain
#7
Won Mah, Sang Man Lee, Jaekwang Lee, Jin Young Bae, Jin Sook Ju, C Justin Lee, Dong Kuk Ahn, Yong Chul Bae
The purinergic receptor P2X3, expressed in the central terminals of primary nociceptive neurons in the brainstem, plays an important role in pathological pain. However, little is known about expression of P2X3 in the brainstem astrocytes and its involvement in craniofacial pathologic pain. To address this issue, we investigated the expression of P2X3 in astrocytes in the trigeminal caudal nucleus (Vc) in a rat model of craniofacial neuropathic pain, chronic constriction injury of infraorbital nerve (CCI-ION)...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29022871/a-postmortem-analysis-of-nmda-ionotropic-and-group-1-metabotropic-glutamate-receptors-in-the-nucleus-accumbens-in-schizophrenia
#8
Jeremy S Lum, Samuel J Millard, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
BACKGROUND: The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort. METHODS: We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms)...
October 6, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29016848/mdm2-mediates-fmrp-and-gp1-mglur-dependent-protein-translation-and-neural-network-activity
#9
Dai-Chi Liu, Joseph Seimetz, Kwan Young Lee, Auinash Kalsotra, Hee Jung Chung, Hua Lu, Nien-Pei Tsai
Activating Group 1 (Gp1) metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, elicits translation-dependent neural plasticity mechanisms that are crucial to animal behavior and circuit development. Dysregulated Gp1 mGluR signaling has been observed in numerous neurological and psychiatric disorders. However, the molecular pathways underlying Gp1 mGluR-dependent plasticity mechanisms are complex and have been elusive. In this study, we identified a novel mechanism through which Gp1 mGluR mediates protein translation and neural plasticity...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28993818/metabotropic-glutamate-receptor-5-and-glutamate-involvement-in-major-depressive-disorder-a-multimodal-imaging-study
#10
Chadi G Abdallah, Jonas Hannestad, Graeme F Mason, Sophie E Holmes, Nicole DellaGioia, Gerard Sanacora, Lihong Jiang, David Matuskey, Ritvij Satodiya, Fabrizio Gasparini, Xin Lin, Jonathan Javitch, Beata Planeta, Nabeel Nabulsi, Richard E Carson, Irina Esterlis
BACKGROUND: Preclinical and postmortem studies have implicated the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of major depressive disorder (MDD). The goal of the present study was to determine the role of mGluR5 in a large group of individuals with MDD compared to healthy controls (HC) in vivo with [(18)F]FPEB and positron emission tomography (PET). Furthermore, we sought to determine the role glutamate plays on mGluR5 availability in MDD. METHODS: Sixty-five participants (30 MDD and 35 HC) completed [(18)F]FPEB PET to estimate the primary outcome measure - mGluR5 volume of distribution (VT), and the secondary outcome measure - mGluR5 distribution volume ratio (DVR)...
July 2017: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/28980941/cerebral-mglur5-availability-contributes-to-elevated-sleep-need-and-behavioral-adjustment-after-sleep-deprivation
#11
Sebastian C Holst, Alexandra Sousek, Katharina Hefti, Sohrab Saberi-Moghadam, Alfred Buck, Simon M Ametamey, Milan Scheidegger, Paul Franken, Anke Henning, Erich Seifritz, Mehdi Tafti, Hans-Peter Landolt
Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need...
October 5, 2017: ELife
https://www.readbyqxmd.com/read/28945221/%C3%AE-synuclein-interacts-with-prp-c-to-induce-cognitive-impairment-through-mglur5-and-nmdar2b
#12
Diana G Ferreira, Mariana Temido-Ferreira, Hugo Vicente Miranda, Vânia L Batalha, Joana E Coelho, Éva M Szegö, Inês Marques-Morgado, Sandra H Vaz, Jeong Seop Rhee, Matthias Schmitz, Inga Zerr, Luísa V Lopes, Tiago F Outeiro
Synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, are neurodegenerative disorders that are characterized by the accumulation of α-synuclein (aSyn) in intracellular inclusions known as Lewy bodies. Prefibrillar soluble aSyn oligomers, rather than larger inclusions, are currently considered to be crucial species underlying synaptic dysfunction. We identified the cellular prion protein (PrP(C)) as a key mediator in aSyn-induced synaptic impairment. The aSyn-associated impairment of long-term potentiation was blocked in Prnp null mice and rescued following PrP(C) blockade...
November 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28914419/social-isolation-during-adolescence-induces-anxiety-behaviors-and-enhances-firing-activity-in-bla-pyramidal-neurons-via-mglur5-upregulation
#13
Song Lin, Xin Li, Yi-Hua Chen, Feng Gao, Hao Chen, Neng-Yuan Hu, Lang Huang, Zheng-Yi Luo, Ji-Hong Liu, Qiang-Long You, Ya-Nan Yin, Ze-Lin Li, Xiao-Wen Li, Zhuo-Jun Du, Jian-Ming Yang, Tian-Ming Gao
Social isolation during the vulnerable period of adolescence contributes to the occurrence of psychiatric disorders and profoundly affects brain development and adult behavior. Although the impact of social isolation during adolescence on anxiety behaviors has been well studied, much less is known about the onset and underlying mechanisms of these behaviors. We observed that following 2 weeks, but not 1 week, of social isolation, adolescent mice exhibited anxiety behaviors. Strikingly, the mGluR5 protein levels in the amygdala increased concomitantly with anxiety behaviors, and both intraperitoneal administration and intra-basolateral amygdala (BLA) infusion of MPEP, a metabotropic glutamate receptor 5 antagonist, normalized anxiety behaviors...
September 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28891868/bivalent-ligand-that-activates-mu-opioid-receptor-and-antagonizes-mglur5-receptor-reduces-neuropathic-pain-in-mice
#14
Cristina D Peterson, Kelley F Kitto, Eyup Akgün, Mary M Lunzer, Maureen S Riedl, Lucy Vulchanova, George L Wilcox, Philip S Portoghese, Carolyn A Fairbanks
The mu opioid receptor (MOR) and metabotropic glutamate receptor 5 (mGluR5) are well-established pharmacological targets in the management of chronic pain. Both receptors are expressed in the spinal cord. MMG22, a bivalent ligand containing 2 pharmacophores separated by 22 atoms, which simultaneously activates MOR and antagonizes mGluR5, has been shown to produce potent reversal of tactile hypersensitivity in rodent models of lipopolysaccharide (LPS)-and bone cancer-induced chronic pain. This study assessed whether intrathecal MMG22 also is effective in reducing pain of neuropathic origin...
December 2017: Pain
https://www.readbyqxmd.com/read/28887860/regulation-of-radial-glial-process-growth-by-glutamate-via-mglur5-trpc3-and-neuregulin-erbb4
#15
Lauri M Louhivuori, Pauli M Turunen, Verna Louhivuori, Venkatram Yellapragada, Tommy Nordström, Per Uhlén, Karl E Åkerman
Radial glial cells play an essential role through their function as guides for neuronal migration during development. Disruption of metabotropic glutamate receptor 5 (mGluR5) function retards the growth of radial glial processes in vitro. Neuregulins (NRG) are activated by proteolytic cleavage and regulate (radial) glial maintenance via ErbB3/ErbB4 receptors. We show here that blocking ErbB4 disrupts radial process extension. Soluble NRG acting on ErbB4 receptors is able to promote radial process extension in particular where process elongation has been impeded by blockade of mGluR5, the nonselective cation channel canonical transient receptor potential 3 (TRPC3), or matrix metalloproteases (MMP)...
January 2018: Glia
https://www.readbyqxmd.com/read/28884874/cerebral-dopaminergic-and-glutamatergic-transmission-relate-to-different-subjective-responses-of-acute-alcohol-intake-an-in-vivo-multimodal-imaging-study
#16
Gil Leurquin-Sterk, Jenny Ceccarini, Cleo Lina Crunelle, Akila Weerasekera, Bart de Laat, Uwe Himmelreich, Guy Bormans, Koen Van Laere
Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single-session [(18) F]fallypride and [(18) F]FPEB positron emission tomography, respectively...
September 8, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28855570/metabotropic-glutamate-receptor-5-deficiency-inhibits-neutrophil-infiltration-after-traumatic-brain-injury-in-mice
#17
Ting Yang, Yang-Wuyue Liu, Li Zhao, Hao Wang, Nan Yang, Shuang-Shuang Dai, Fengtian He
Both brain native inflammatory cells and infiltrated peripheral white blood cells (WBCs) are primary participants in the brain inflammatory damage post-TBI. Metabotropic glutamate receptor 5 (mGluR5) has been reported to regulate microglias and astrocytes to affect inflammation after TBI, but its effect on modulating infiltrated peripheral WBCs remains unclear. In a mouse moderate TBI model, we found that mGluR5 knockout (KO) significantly reduced neutrophil infiltration and inflammatory cytokine expression in the brain at 24 hours post TBI, which was accompanied by improved neurological dysfunction...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851991/upregulation-of-prefrontal-metabotropic-glutamate-receptor-5-mediates-neuropathic-pain-and-negative-mood-symptoms-after-spinal-nerve-injury-in-rats
#18
Geehoon Chung, Chae Young Kim, Yeong-Chan Yun, Sang Ho Yoon, Myoung-Hwan Kim, Yu Kyeong Kim, Sang Jeong Kim
Patients with chronic pain easily accompany the negative mood symptoms such as depression and anxiety, and these disturbances in turn affect the aversive perception of pain. However, the underlying mechanisms are largely unknown. We hypothesized that the alteration of metabotropic glutamate receptor 5 (mGluR5) in the brain region underlies such a comorbidity of aversive states. We scanned the brain of chronic neuropathic pain model rats using positron emission tomography (PET) technique with an mGluR5-selective radiotracer [11C] ABP688 and found various brain regions with higher or lower level of mGluR5 compared to control rats...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28825789/multifunctional-analogs-of-kynurenic-acid-for-the-treatment-of-alzheimer-s-disease-synthesis-pharmacology-and-molecular-modeling-studies
#19
Girdhar Singh Deora, Srinivas Kantham, Stephen Chan, Satish N Dighe, Suresh K Veliyath, Gawain McColl, Marie-Odile Parat, Ross P McGeary, Benjamin P Ross
We report the synthesis and pharmacological investigation of analogs of the endogenous molecule kynurenic acid (KYNA) as multifunctional agents for the treatment of Alzheimer's disease (AD). Synthesized KYNA analogs were tested for their N-methyl-d-aspartate (NMDA) receptor binding, mGluR5 binding and function, acetylcholinesterase (AChE) inhibition, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, interference with the amyloid β peptide (Aβ) fibrillation process, and protection against Aβ-induced toxicity in transgenic Caenorhabditis elegans strain GMC101 expressing full-length Aβ42...
September 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28821676/brief-novel-visual-experience-fundamentally-changes-synaptic-plasticity-in-the-mouse-visual-cortex
#20
Shuo Li, Laijian Wang, Xiaoxiu Tie, Kazuhiro Sohya, Xian Lin, Alfredo Kirkwood, Bin Jiang
LTP has been known to be a mechanism by which experience modifies synaptic responses in the neocortex. Visual deprivation in the form of dark exposure or dark rearing from birth enhances NMDAR-dependent LTP in layer 2/3 of visual cortex, a process often termed metaplasticity, which may involve changes in NMDAR subunit composition and function. However, the effects of reexposure to light after dark rearing from birth on LTP induction have not been explored. Here, we showed that the light exposure after dark rearing revealed a novel NMDAR independent form of LTP in the layer 2/3 pyramidal cells in visual cortex of mice of both sexes, which is dependent on mGluR5 activation and is associated with intracellular Ca(2+) rise, CaMKII activity, PKC activity, and intact protein synthesis...
September 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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