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https://www.readbyqxmd.com/read/29875641/an-integrative-neuroscience-framework-for-the-treatment-of-chronic-pain-from-cellular-alterations-to-behavior
#1
Jess D Greenwald, Keith M Shafritz
Chronic pain can result from many pain syndromes including complex regional pain syndrome (CRPS), phantom limb pain and chronic low back pain, among others. On a molecular level, chronic pain syndromes arise from hypersensitization within the dorsal horn of the spinal cord, a process known as central sensitization. Central sensitization involves an upregulation of ionotropic and metabotropic glutamate receptors (mGluRs) similar to that of long-term potentiation (LTP). Regions of the brain in which LTP occurs, such as the amygdala and hippocampus, are implicated in fear- and memory-related brain circuity...
2018: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29861284/the-temporal-dynamics-of-arc-expression-regulate-cognitive-flexibility
#2
Mark J Wall, Dawn R Collins, Samantha L Chery, Zachary D Allen, Elissa D Pastuzyn, Arlene J George, Viktoriya D Nikolova, Sheryl S Moy, Benjamin D Philpot, Jason D Shepherd, Jürgen Müller, Michael D Ehlers, Angela M Mabb, Sonia A L Corrêa
Neuronal activity regulates the transcription and translation of the immediate-early gene Arc/Arg3.1, a key mediator of synaptic plasticity. Proteasome-dependent degradation of Arc tightly limits its temporal expression, yet the significance of this regulation remains unknown. We disrupted the temporal control of Arc degradation by creating an Arc knockin mouse (ArcKR) where the predominant Arc ubiquitination sites were mutated. ArcKR mice had intact spatial learning but showed specific deficits in selecting an optimal strategy during reversal learning...
May 24, 2018: Neuron
https://www.readbyqxmd.com/read/29849054/metaplasticity-contributes-to-memory-formation-in-the-hippocampus
#3
Ana P Crestani, Jamie N Krueger, Eden V Barragan, Yuki Nakazawa, Sonya E Nemes, Jorge A Quillfeldt, John A Gray, Brian J Wiltgen
Prior learning can modify the plasticity mechanisms that are used to encode new information. For example, NMDA receptor (NMDAR) activation is typically required for new spatial and contextual learning in the hippocampus. However, once animals have acquired this information, they can learn new tasks even if NMDARs are blocked. This finding suggests that behavioral training alters cellular plasticity mechanisms such that NMDARs are not required for subsequent learning. The mechanisms that mediate this change are currently unknown...
May 16, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29800675/intra-accumbal-administration-of-amn082-a-metabotropic-glutamate-receptor-type-7-allosteric-agonist-inhibits-the-acquisition-but-not-the-expression-of-morphine-induced-conditioned-place-preference-in-rats
#4
Mahsaneh Vatankhah, Saeideh Karimi-Haghighi, Abdolrahman Sarihi, Abbas Haghparast
The nucleus accumbens (NAc) plays a primary role in opioid reward. The actions of glutamate are mediated by the activation of ionotropic and metabotropic glutamate receptors (mGluRs). Previous documents have shown the extensive distributions of the different types of mGluRs, including mGluR7, in regions that are involved in opioid reward, such as the NAc. In this study, seventy male Wistar rats were used to investigate the role of mGluR7 receptors in the NAc on the acquisition and expression of morphine-induced conditioned place preference (CPP)...
May 22, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29793411/neuropharmacological-screening-of-chiral-and-non-chiral-phthalimidecontaining-compounds-in-mice-in-vivo-and-in-silico-experiments
#5
Carolina Campos-Rodriguez, Jose G Trujillo-Ferrara, Ameyali Alvarez-Guerra, Iran M Cumbres Vargas, Roberto I Cuevas-Hernandez, Erik Andrade-Jorge, Sergio Zamudio, Eduardo Ramirez-San Juan
BACKGROUND: Thalidomide, the first synthesized phthalimide, has demonstrated sedative-hypnotic and antiepileptic effects on the central nervous system. N-substituted phthalimides have an interesting chemical structure that confers important biological properties. OBJECTIVE: Non-chiral (ortho and para bis-isoindoline-1,3-dione, phthaloylglycine) and chiral phthalimides (N-substituted with aspartate or glutamate) were synthesized and the sedative, anxiolytic and anticonvulsant effects were tested...
May 24, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29786082/mtorc2-but-not-mtorc1-is-required-for-hippocampal-mglur-ltd-and-associated-behaviors
#6
Ping Jun Zhu, Chien-Ju Chen, Jacqunae Mays, Loredana Stoica, Mauro Costa-Mattioli
The mechanistic target of rapamycin complex 1 (mTORC1) has been reported to be necessary for metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). Here we found that mTORC1-deficient mice exhibit normal hippocampal mGluR-LTD and associated behaviors. Moreover, rapamycin blocks mGluR-LTD in mTORC1-deficient mice. However, both rapamycin and mGluR activation regulate mTOR complex 2 (mTORC2) activity, and mTORC2-deficient mice show impaired mGluR-LTD and associated behaviors. Thus, mTORC2 is a major regulator of mGluR-LTD...
May 21, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29777761/functional-organization-of-postsynaptic-glutamate-receptors
#7
REVIEW
Nicky Scheefhals, Harold D MacGillavry
Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29753887/peri-adolescent-drinking-of-ethanol-and-or-nicotine-modulates-astroglial-glutamate-transporters-and-metabotropic-glutamate-receptor-1-in-female-alcohol-preferring-rats
#8
Fawaz Alasmari, Richard L Bell, P S S Rao, Alaa M Hammad, Youssef Sari
Impairment in glutamate neurotransmission mediates the development of dependence upon nicotine (NIC) and ethanol (EtOH). Previous work indicated that continuous access to EtOH or phasic exposure to NIC reduces expression of the glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT) but not the glutamate/aspartate transporter (GLAST). Additionally, metabotropic glutamate receptors (mGluRs) expression was affected following exposure to EtOH or NIC. However, little is known about the effects of EtOH and NIC co-consumption on GLT-1, xCT, GLAST, and mGluR1 expression...
May 10, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29753314/allosteric-and-orthosteric-activators-of-mglur8-differentially-affect-the-chemotherapeutic-induced-human-neuroblastoma-sh-sy5y-cell-damage-the-impact-of-cell-differentiation-state
#9
Danuta Jantas, Beata Grygier, Justyna Zatorska, Władysław Lasoń
The participation of group III metabotropic glutamate receptors (mGluRs) in cancer growth and progression is still an understudied issue. Based on our recent data on high expression of mGluR8 in human neuroblastoma SH-SY5Y cells, in the present study we evaluated the effect of an mGluR8-specific positive allosteric modulator (PAM: AZ12216052) and orthosteric agonist ((S)-3,4-DCPG) on chemotherapeutic (doxorubicin, irinotecan or cisplatin)-evoked cell damage in undifferentiated (UN-) and retinoic acid-differentiated (RA-) SH-SY5Y cells...
May 12, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29689337/gender-specific-desensitization-of-group-i-metabotropic-glutamate-receptors-after-maternal-l-glutamate-intake-during-lactation
#10
Antonio López-Zapata, David Agustín León-Navarro, María Crespo, Mairena Martín
In the present work we have studied the effect of maternal intake of l-Glutamate (l-Glu) (1 g/L) during lactation on group I mGluR transduction pathway in brain plasma membrane from 15 days-old neonates. Results obtained have shown that maternal l-glutamate intake did not significantly affect neither weights of pups nor negative geotaxis reflex, an index of neurobehavioral development, but increased l-Glu plasma level in both male and female neonates. In male neonates, maternal l-Glu intake evoked a loss of mGluR1 whereas no variation on mGluR5 was observed as revealed by Western-blotting assay...
April 21, 2018: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29686062/synaptic-adhesion-protein-elfn1-is-a-selective-allosteric-modulator-of-group-iii-metabotropic-glutamate-receptors-in-trans
#11
Henry A Dunn, Dipak N Patil, Yan Cao, Cesare Orlandi, Kirill A Martemyanov
Functional characterization of the GPCR interactome has been focused predominantly on intracellular interactions, yet GPCRs are increasingly found in complex with extracellular proteins. Extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) was recently reported to physically anchor mGluR6 and mGluR7 across retinal and hippocampal synapses, respectively; however, the consequence of transsynaptic interactions on properties and pharmacology of these receptors are unknown. In the current study, we explore the effects of ELFN1 on mGluR signaling and pharmacology...
May 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29670176/activity-dependent-modulation-of-hippocampal-synaptic-plasticity-via-pirb-and-endocannabinoids
#12
Maja Djurisic, Barbara K Brott, Nay L Saw, Mehrdad Shamloo, Carla J Shatz
The threshold for Hebbian synaptic plasticity in the CNS is modulated by prior synaptic activity. At adult CA3-CA1 synapses, endocannabinoids play a role in this process, but how activity engages and maintains this retrograde signaling system is not well understood. Here we show that conditional deletion of Paired Immunoglobulin-like receptor B (PirB) from pyramidal neurons in adult mouse hippocampus results in deficient LTD at CA3-CA1 synapses over a range of stimulation frequencies, accompanied by an increase in LTP...
April 18, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29651456/systematic-reconstruction-of-autism-biology-from-massive-genetic-mutation-profiles
#13
Weijun Luo, Chaolin Zhang, Yong-Hui Jiang, Cory R Brouwer
Autism spectrum disorder (ASD) affects 1% of world population and has become a pressing medical and social problem worldwide. As a paradigmatic complex genetic disease, ASD has been intensively studied and thousands of gene mutations have been reported. Because these mutations rarely recur, it is difficult to (i) pinpoint the fewer disease-causing versus majority random events and (ii) replicate or verify independent studies. A coherent and systematic understanding of autism biology has not been achieved. We analyzed 3392 and 4792 autism-related mutations from two large-scale whole-exome studies across multiple resolution levels, that is, variants (single-nucleotide), genes (protein-coding unit), and pathways (molecular module)...
April 2018: Science Advances
https://www.readbyqxmd.com/read/29627342/blockade-of-%C3%AE-2-adrenergic-or-metabotropic-glutamate-receptors-induces-glutamate-release-in-the-locus-coeruleus-to-activate-descending-inhibition-in-rats-with-chronic-neuropathic-hypersensitivity
#14
Ken-Ichiro Hayashida, Masafumi Kimuram, James C Eisenach
Locus coeruleus (LC)-spinal noradrenergic projections are important to endogenous analgesic mechanisms and can be activated by local glutamate signaling in the LC. The current study examined the local glutamatergic, GABAergic, and noradrenergic influences on glutamate release in the LC and noradrenergic descending inhibition in rats 6 weeks after spinal nerve ligation (SNL). Intra-LC injection of the α2 adrenoceptor antagonist idazoxan or the group 2 metabotropic glutamate receptor (mGluR) antagonist (RS)-α-Methyl-4-tetrazolylphenylglycine (MTPG) increased withdrawal thresholds in SNL animals and this was reversed by the blockade of α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) receptors in the LC or α2-adrenoceptors in the spinal cord, but not in normal animals...
May 29, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29625424/mglu-receptors-in-the-treatment-of-parkinson-s-disease-and-l-dopa-induced-dyskinesia
#15
REVIEW
Irene Sebastianutto, Maria Angela Cenci
Parkinson's disease (PD) is a neurodegenerative disorder characterized by typical motor features that result from dopamine (DA) depletion in the striatum. DA replacement therapy with L-DOPA is the most efficacious symptomatic treatment, but causes complications that limit its utility, in particular, L-DOPA-induced dyskinesia (LID). LID is primarily caused by pre-synaptic and post-synaptic changes in DA neurotransmission, although it also depends on altered glutamatergic transmission at several nodes of the cortico-basal ganglia-thalamocortical network...
February 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29617377/inositol-1-4-5-trisphosphate-3-kinase-a-overexpressed-in-mouse-forebrain-modulates-synaptic-transmission-and-mglur-ltd-of-ca1-pyramidal-neurons
#16
Byungil Choi, Hyun Woo Lee, Seojung Mo, Jin Yong Kim, Hyun Wook Kim, Im Joo Rhyu, Eunhwa Hong, Yeon Kyung Lee, June-Seek Choi, Chong-Hyun Kim, Hyun Kim
Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP3) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP3K-A binds to F-actin in an activity-dependent manner and accumulates in dendritic spines, where it is involved in the regulation of synaptic plasticity. IP3K-A knockout mice exhibit deficits in some forms of hippocampus-dependent learning and synaptic plasticity, such as long-term potentiation in the dentate gyrus synapses of the hippocampus...
2018: PloS One
https://www.readbyqxmd.com/read/29614089/hippocampal-protein-kinase-d1-is-necessary-for-dhpg-induced-learning-and-memory-impairments-in-rats
#17
Wei Wang, Florian Duclot, Bradley R Groveman, Nicole Carrier, Haifa Qiao, Xiao-Qian Fang, Hui Wang, Wenkuan Xin, Xing-Hong Jiang, Michael W Salter, Xin-Sheng Ding, Mohamed Kabbaj, Xian-Min Yu
BACKGROUND: Understanding molecular mechanisms underlying the induction of learning and memory impairments remains a challenge. Recent investigations have shown that the activation of group I mGluRs (mGluR1 and mGluR5) in cultured hippocampal neurons by application of (S)-3,5-Dihydroxyphenylglycine (DHPG) causes the regulated internalization of N-methyl-D-aspartate receptors (NMDARs), which subsequently activates protein kinase D1 (PKD1). Through phosphorylating the C-terminals of the NMDAR GluN2 subunits, PKD1 down-regulates the activity of remaining (non-internalized) surface NMDARs...
2018: PloS One
https://www.readbyqxmd.com/read/29605730/metabotropic-glutamate-receptors-targets-for-neuroprotective-therapies-in-parkinson-disease
#18
REVIEW
Gunasingh J Masilamoni, Yoland Smith
Metabotropic glutamate receptors (mGluRs) are heavily expressed throughout the basal ganglia (BG), where they modulate neuronal excitability, transmitter release and long term synaptic plasticity. Therefore, targeting specific mGluR subtypes by means of selective drugs could be a possible strategy for restoring normal synaptic function and neuronal activity of the BG in Parkinson disease (PD). Preclinical studies have revealed that specific mGluR subtypes mediate significant neuroprotective effects that reduce toxin-induced midbrain dopaminergic neuronal death in animal models of PD...
February 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29605484/amn082-a-metabotropic-glutamate-receptor-type-7-allosteric-agonist-in-the-nac-facilitates-extinction-and-inhibits-the-reinstatement-of-morphine-induced-conditioned-place-preference-in-male-rats
#19
Mahsaneh Vatankhah, Abdolrahman Sarihi, Alireza Komaki, Siamak Shahidi, Abbas Haghparast
Nucleus accumbens (NAc) plays a primary role in opioid reward. The actions of glutamate (which is the most extensive excitatory neurotransmitter in the mammalian central nervous system) are mediated through the activation of the ionotropic and metabotropic glutamate receptors (mGluRs). Previous studies have shown the extensive distributions of the different types of mGluRs, including mGluR7, in regions that are involved in opioid reward, such as NAc. In this study, CPP was used to investigate the effect of mGluR7 on the extinction period, and the reinstatement of morphine...
March 29, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29593596/neural-dynamics-of-autistic-repetitive-behaviors-and-fragile-x-syndrome-basal-ganglia-movement-gating-and-mglur-modulated-adaptively-timed-learning
#20
Stephen Grossberg, Devika Kishnan
This article develops the iSTART neural model that proposes how specific imbalances in cognitive, emotional, timing, and motor processes that involve brain regions like prefrontal cortex, temporal cortex, amygdala, hypothalamus, hippocampus, and cerebellum may interact together to cause behavioral symptoms of autism. These imbalances include underaroused emotional depression in the amygdala/hypothalamus, learning of hyperspecific recognition categories that help to cause narrowly focused attention in temporal and prefrontal cortices, and breakdowns of adaptively timed motivated attention and motor circuits in the hippocampus and cerebellum...
2018: Frontiers in Psychology
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