keyword
https://read.qxmd.com/read/38339206/neuropharmacological-evidence-implicating-drug-induced-glutamate-receptor-dysfunction-in-affective-and-cognitive-sequelae-of-subchronic-methamphetamine-self-administration-in-mice
#1
JOURNAL ARTICLE
Christopher J E Denning, Lauren E Madory, Jessica N Herbert, Ryan A Cabrera, Karen K Szumlinski
Methamphetamine (MA) is a highly addictive drug, and MA use disorder is often comorbid with anxiety and cognitive impairment. These comorbid conditions are theorized to reflect glutamate-related neurotoxicity within the frontal cortical regions. However, our prior studies of MA-sensitized mice indicate that subchronic, behaviorally non-contingent MA treatment is sufficient to dysregulate glutamate transmission in mouse brain. Here, we extend this prior work to a mouse model of high-dose oral MA self-administration (0...
February 5, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38297084/src-family-kinase-inhibition-rescues-molecular-and-behavioral-phenotypes-but-not-protein-interaction-network-dynamics-in-a-mouse-model-of-fragile-x-syndrome
#2
JOURNAL ARTICLE
Vera Stamenkovic, Jonathan D Lautz, Felicia M Harsh, Stephen E P Smith
Glutamatergic synapses encode information from extracellular inputs using dynamic protein interaction networks (PINs) that undergo widespread reorganization following synaptic activity, allowing cells to distinguish between signaling inputs and generate coordinated cellular responses. Here, we investigate how Fragile X Messenger Ribonucleoprotein (FMRP) deficiency disrupts signal transduction through a glutamatergic synapse PIN downstream of NMDA receptor or metabotropic glutamate receptor (mGluR) stimulation...
January 31, 2024: Molecular Psychiatry
https://read.qxmd.com/read/38244260/cyclooxygenase-2-inhibition-affects-the-ratio-of-glun2a-glun2b-receptor-subunits-through-interaction-with-mglur5-in-the-mouse-brain
#3
JOURNAL ARTICLE
Katarzyna Stachowicz, Patrycja Pańczyszyn-Trzewik, Paulina Misztak, Szymon Rzeźniczek, Magdalena Sowa-Kućma
N-methyl-D-aspartic acid receptors (NMDARs) are the most studied receptors in mammalian brains. Their role in depression, cognition, schizophrenia, learning and memorization, Alzheimer's disease, and more is well documented. In the search for new drug candidates in depression, intensive studies have been conducted. Compounds that act by influencing NMDARs have been particularly intensively investigated following the success of ketamine in clinics. Unfortunately, the side effects associated with ketamine do not allow it to be useful in all cases...
January 17, 2024: Neuropeptides
https://read.qxmd.com/read/37348610/anxiolytic-like-effects-of-an-mglur-5-antagonist-and-a-mglur-2-3-agonist-and-antidepressant-like-effects-of-an-mglur-7-agonist-in-the-chick-social-separation-stress-test-a-dual-drug-screening-model-of-treatment-resistant-depression
#4
JOURNAL ARTICLE
Stephen W White, Gwendolyn D Squires, Sequioa J Smith, Gwendolyn M Wright, Kenneth J Sufka, John M Rimoldi, Rama S Gadepalli
Modulation of glutamate receptors has demonstrated anxiolytic and/or antidepressant effects in rodent stress models. The chick social-separation stress paradigm exposes socially raised aves to an isolation stressor which elicits distress vocalizations (DVocs) in an attempt to re-establish contact. The model presents a state of panic during the first 5 min followed by a state of behavioral despair during the last 60 to 90 min. Making it useful as a dual anxiolytic/antidepressant screening assay. Further research has identified the Black Australorp strain as a stress-vulnerable, treatment-resistant, and ketamine-sensitive genetic line...
June 20, 2023: Pharmacology, Biochemistry, and Behavior
https://read.qxmd.com/read/37238731/enhanced-l-%C3%AE-aminoisobutyric-acid-is-involved-in-the-pathophysiology-of-effectiveness-for-treatment-resistant-schizophrenia-and-adverse-reactions-of-clozapine
#5
JOURNAL ARTICLE
Kouji Fukuyama, Eishi Motomura, Motohiro Okada
Clozapine is an effective antipsychotic for the treatment of antipsychotic-resistant schizophrenia; however, specific types of A/B adverse effects and clozapine-discontinuation syndromes are also well known. To date, both the critical mechanisms of clinical actions (effective for antipsychotic-resistant schizophrenia) and the adverse effects of clozapine remain to be elucidated. Recently, we demonstrated that clozapine increased the synthesis of L-β-aminoisobutyric acid (L-BAIBA) in the hypothalamus. L-BAIBA is an activator of the adenosine monophosphate-activated protein kinase (AMPK), glycine receptor, GABAA receptor, and GABAB receptor (GABAB -R)...
May 19, 2023: Biomolecules
https://read.qxmd.com/read/37175959/pharmacological-modulation-of-excitotoxicity-through-the-combined-use-of-nmda-receptor-inhibition-and-group-iii-mglu-activation-reduces-tmt-induced-neurodegeneration-in-the-rat-hippocampus
#6
JOURNAL ARTICLE
Ekaterina V Pershina, Irina Yu Chernomorets, Dmitry A Fedorov, Vladimir I Arkhipov
We studied the neuroprotective properties of the non-competitive NMDA receptor antagonist memantine, in combination with a positive allosteric modulator of metabotropic glutamate receptors of Group III, VU 0422288. The treatment was started 48 h after the injection of neurotoxic agent trimethyltin (TMT) at 7.5 mg/kg. Three weeks after TMT injection, functional and morphological changes in a rat hippocampus were evaluated, including the expression level of genes characterizing glutamate transmission and neuroinflammation, animal behavior, and hippocampal cell morphology...
May 4, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37091922/target-cell-specific-plasticity-rules-of-nmda-receptor-mediated-synaptic-transmission-in-the-hippocampus
#7
JOURNAL ARTICLE
Stefano Lutzu, Karina Alviña, Nagore Puente, Pedro Grandes, Pablo E Castillo
Long-term potentiation and depression of NMDA receptor-mediated synaptic transmission (NMDAR LTP/LTD) can significantly impact synapse function and information transfer in several brain areas. However, the mechanisms that determine the direction of NMDAR plasticity are poorly understood. Here, using physiologically relevant patterns of presynaptic and postsynaptic burst activities, whole-cell patch clamp recordings, 2-photon laser calcium imaging in acute rat hippocampal slices and immunoelectron microscopy, we tested whether distinct calcium dynamics and group I metabotropic glutamate receptor (I-mGluR) subtypes control the sign of NMDAR plasticity...
2023: Frontiers in Cellular Neuroscience
https://read.qxmd.com/read/36979762/the-role-of-glutamate-receptors-in-epilepsy
#8
REVIEW
Tsang-Shan Chen, Tzu-Hsin Huang, Ming-Chi Lai, Chin-Wei Huang
Glutamate is an essential excitatory neurotransmitter in the central nervous system, playing an indispensable role in neuronal development and memory formation. The dysregulation of glutamate receptors and the glutamatergic system is involved in numerous neurological and psychiatric disorders, especially epilepsy. There are two main classes of glutamate receptor, namely ionotropic and metabotropic (mGluRs) receptors. The former stimulate fast excitatory neurotransmission, are N -methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and kainate; while the latter are G-protein-coupled receptors that mediate glutamatergic activity via intracellular messenger systems...
March 4, 2023: Biomedicines
https://read.qxmd.com/read/36937569/mglur-dependent-plasticity-in-rodent-models-of-alzheimer-s-disease
#9
JOURNAL ARTICLE
Gonzalo Valdivia, Alvaro O Ardiles, Abimbola Idowu, Claudia Salazar, Hey-Kyoung Lee, Michela Gallagher, Adrian G Palacios, Alfredo Kirkwood
Long-term potentiation (LTP) and depression (LTD) are currently the most comprehensive models of synaptic plasticity models to subserve learning and memory. In the CA1 region of the hippocampus LTP and LTD can be induced by the activation of either NMDA receptors or mGluR5 metabotropic glutamate receptors. Alterations in either form of synaptic plasticity, NMDAR-dependent or mGluR-dependent, are attractive candidates to contribute to learning deficits in conditions like Alzheimer's disease (AD) and aging. Research, however, has focused predominantly on NMDAR-dependent forms of LTP and LTD...
2023: Frontiers in Synaptic Neuroscience
https://read.qxmd.com/read/35872016/camkii-t286-phosphorylation-has-distinct-essential-functions-in-three-forms-of-long-term-plasticity
#10
JOURNAL ARTICLE
Sarah G Cook, Nicole L Rumian, K Ulrich Bayer
The Ca2+ /calmodulin-dependent protein kinase II (CaMKII) mediates long-term potentiation or depression (LTP or LTD) after distinct stimuli of hippocampal NMDA-type glutamate receptors (NMDARs). NMDAR-dependent LTD prevails in juvenile mice, but a mechanistically different form of LTD can be readily induced in adults by instead stimulating metabotropic glutamate receptors (mGluRs). However, the role that CaMKII plays in the mGluR-dependent form of LTD is not clear. Here we show that mGluR-dependent LTD also requires CaMKII and its T286 autophosphorylation (pT286), which induces Ca2+ -independent autonomous kinase activity...
July 21, 2022: Journal of Biological Chemistry
https://read.qxmd.com/read/35615440/selective-recruitment-of-presynaptic-and-postsynaptic-forms-of-mglur-ltd
#11
JOURNAL ARTICLE
Thomas M Sanderson, Liam T Ralph, Mascia Amici, Ai Na Ng, Bong-Kiun Kaang, Min Zhuo, Sang Jeong Kim, John Georgiou, Graham L Collingridge
In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with the selective agonist DHPG. There is evidence that mGluR-LTD can be expressed by either a decrease in the probability of neurotransmitter release [P(r)] or by a change in postsynaptic AMPA receptor number. However, what determines the locus of expression is unknown. We investigated the expression mechanisms of mGluR-LTD using either a low (30 μM) or a high (100 μM) concentration of (RS)-DHPG...
2022: Frontiers in Synaptic Neuroscience
https://read.qxmd.com/read/35484241/bioactive-human-alzheimer-brain-soluble-a%C3%AE-pathophysiology-and-therapeutic-opportunities
#12
REVIEW
Shaomin Li, Andrew M Stern
The accumulation of amyloid-β protein (Aβ) plays an early role in the pathogenesis of Alzheimer's disease (AD). The precise mechanism of how Aβ accumulation leads to synaptic dysfunction and cognitive impairment remains unclear but is likely due to small soluble oligomers of Aβ (oAβ). Most studies have used chemical synthetic or cell-secreted Aβ oligomers to study their pathogenic mechanisms, but the Aβ derived from human AD brain tissue is less well characterized. Here we review updated knowledge on the extraction and characterization of bioactive human AD brain oAβ and the mechanisms by which they cause hippocampal synaptic dysfunction...
April 28, 2022: Molecular Psychiatry
https://read.qxmd.com/read/35326498/non-linear-frequency-dependence-of-neurovascular-coupling-in-the-cerebellar-cortex-implies-vasodilation-vasoconstriction-competition
#13
JOURNAL ARTICLE
Giuseppe Gagliano, Anita Monteverdi, Stefano Casali, Umberto Laforenza, Claudia A M Gandini Wheeler-Kingshott, Egidio D'Angelo, Lisa Mapelli
Neurovascular coupling (NVC) is the process associating local cerebral blood flow (CBF) to neuronal activity (NA). Although NVC provides the basis for the blood oxygen level dependent (BOLD) effect used in functional MRI (fMRI), the relationship between NVC and NA is still unclear. Since recent studies reported cerebellar non-linearities in BOLD signals during motor tasks execution, we investigated the NVC/NA relationship using a range of input frequencies in acute mouse cerebellar slices of vermis and hemisphere...
March 19, 2022: Cells
https://read.qxmd.com/read/34999011/the-glutamatergic-synapse-a-key-hub-in-neuronal-metabolism-signalling-and-plasticity
#14
EDITORIAL
Bruno G Frenguelli
The Special Issue of Neuropharmacology on the glutamatergic synapse is one of a series of Special Issues celebrating the 40th anniversary of Dick Evans and Jeff Watkins's seminal review on excitatory amino acids (Watkins and Evans, 1981). Through a careful appraisal of the literature extending several decades prior to the 1980s, and their own development and use of ligands for excitatory amino acid receptors, Dick and Jeff provided incontrovertible proof for the veracity and importance of glutamate as a neurotransmitter in the central nervous system...
April 1, 2022: Neuropharmacology
https://read.qxmd.com/read/34919905/glutamate-receptors-and-synaptic-plasticity-the-impact-of-evans-and-watkins
#15
REVIEW
G L Collingridge, W C Abraham
On the occasion of the 40 year anniversary of the hugely impactful review by Richard (Dick) Evans and Jeff Watkins, we describe how their work has impacted the field of synaptic plasticity. We describe their influence in each of the major glutamate receptor subtypes: AMPARs, NMDARs, KARs and mGluRs. Particular emphasis is placed on how their work impacted our own studies in the hippocampus. For example, we describe how the tools and regulators that they identified for studying NMDARs (e.g., NMDA, D-AP5 and Mg2+ ) led to the understanding of the molecular basis of the induction of LTP...
March 15, 2022: Neuropharmacology
https://read.qxmd.com/read/34788607/homer1a-regulates-shank3-expression-and-underlies-behavioral-vulnerability-to-stress-in-a-model-of-phelan-mcdermid-syndrome
#16
JOURNAL ARTICLE
Raozhou Lin, Lisa N Learman, M Ali Bangash, Tatiana Melnikova, Erica Leyder, Sai C Reddy, Nirinjini Naidoo, Joo Min Park, Alena Savonenko, Paul F Worley
Mutations of SHANK3 cause Phelan-McDermid syndrome (PMS), and these individuals can exhibit sensitivity to stress, resulting in behavioral deterioration. Here, we examine the interaction of stress with genotype using a mouse model with face validity to PMS. In Shank3ΔC/+ mice, swim stress produces an altered transcriptomic response in pyramidal neurons that impacts genes and pathways involved in synaptic function, signaling, and protein turnover. Homer1a, which is part of the Shank3-mGluR-N-methyl-D-aspartate (NMDA) receptor complex, is super-induced and is implicated in the stress response because stress-induced social deficits in Shank3ΔC/+ mice are mitigated in Shank3ΔC/+ ;Homer1a-/- mice...
November 16, 2021: Cell Reports
https://read.qxmd.com/read/34664085/the-na-activated-k-channel-slack-contributes-to-synaptic-development-and-plasticity
#17
JOURNAL ARTICLE
Lucas Matt, Thomas Pham, David Skrabak, Felix Hoffmann, Philipp Eckert, Jiaqi Yin, Miriam Gisevius, Rebekka Ehinger, Anne Bausch, Marius Ueffing, Karsten Boldt, Peter Ruth, Robert Lukowski
Human mutations of the Na+ -activated K+ channel Slack (KCNT1) are associated with epilepsy and intellectual disability. Accordingly, Slack knockout mice (Slack-/- ) exhibit cognitive flexibility deficits in distinct behavioral tasks. So far, however, the underlying causes as well as the role of Slack in hippocampus-dependent memory functions remain enigmatic. We now report that infant (P6-P14) Slack-/- lack both hippocampal LTD and LTP, likely due to impaired NMDA receptor (NMDAR) signaling. Postsynaptic GluN2B levels are reduced in infant Slack-/- , evidenced by lower amplitudes of NMDAR-meditated excitatory postsynaptic potentials...
December 2021: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/34625112/activation-of-plc%C3%AE-1-enhances-endocannabinoid-mobilization-to-restore-hippocampal-spike-timing-dependent-potentiation-and-contextual-fear-memory-impaired-by-alzheimer-s-amyloidosis
#18
JOURNAL ARTICLE
Jaedong Lee, Jeehyun Kwag
BACKGROUND: Accumulation of amyloid beta oligomers (AβO) in Alzheimer's disease (AD) impairs hippocampal long-term potentiation (LTP), leading to memory deficits. Thus, identifying the molecular targets of AβO involved in LTP inhibition is critical for developing therapeutics for AD. Endocannabinoid (eCB) synthesis and release, a process collectively called eCB mobilization by hippocampal CA1 pyramidal cells, is known to facilitate LTP induction. eCB can be mobilized either by postsynaptic depolarization in an intracellular Ca2+ concentration ([Ca2+ ]i )-dependent pathway or by group 1 metabotropic glutamate receptor (mGluR) activation in a phospholipase Cβ (PLCβ)-dependent pathway...
October 8, 2021: Alzheimer's Research & Therapy
https://read.qxmd.com/read/34553130/sustained-postsynaptic-kainate-receptor-activation-downregulates-ampa-receptor-surface-expression-and-induces-hippocampal-ltd
#19
JOURNAL ARTICLE
Jithin D Nair, Ellen Braksator, Busra P Yucel, Alexandra Fletcher-Jones, Richard Seager, Jack R Mellor, Zafar I Bashir, Kevin A Wilkinson, Jeremy M Henley
It is well established that long-term depression (LTD) can be initiated by either NMDA or mGluR activation. Here we report that sustained activation of GluK2 subunit-containing kainate receptors (KARs) leads to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) endocytosis and induces LTD of AMPARs (KAR-LTDAMPAR ) in hippocampal neurons. The KAR-evoked loss of surface AMPARs is blocked by the ionotropic KAR inhibitor UBP 310 indicating that KAR-LTDAMPAR requires KAR channel activity. Interestingly, however, blockade of PKC or PKA also reduces GluA2 surface expression and occludes the effect of KAR activation...
September 24, 2021: IScience
https://read.qxmd.com/read/34526080/brain-derived-neurotrophic-factor-produced-long-term-synaptic-enhancement-in-the-anterior-cingulate-cortex-of-adult-mice
#20
JOURNAL ARTICLE
Hui-Hui Miao, Zhuang Miao, Ji-Gang Pan, Xu-Hui Li, Min Zhuo
Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) is one of the diffusible messengers for enhancing synaptic transmission in the hippocampus. Less information is available about the possible roles of BDNF in the anterior cingulate cortex (ACC). In the present study, we used 64-electrode array field recording system to investigate the effect of BDNF on ACC excitatory transmission. We found that BDNF enhanced synaptic responses in a dose-dependent manner in the ACC in C57/BL6 mice...
September 15, 2021: Molecular Brain
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