Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior

Gee, Christine E.; Peterlik, Daniel; Neuhäuser, Christoph; Bouhelal, Rochdi; Kaupmann, Klemens; Laue, Grit; Uschold-Schmidt, Nicole; Feuerbach, Dominik; Zimmermann, Kaspar; Ofner, Silvio; Cryan, John F.; Putten, Herman van der; Fendt, Markus; Vranesic, Ivo; Glatthar, Ralf; Flor, Peter J.

doi:10.1074/jbc.m113.542654

Cited by 65 publications

(71 citation statements)

References 61 publications

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“…Furthermore, GRM7 is involved in many processes, such as stress, memory, reward control, circadian activity [2] and brain emotion circuits [5]. O'Connor et al reported that siRNA-induced knock-down of GRM7 reduces anxiety in the mouse [22].…”

Section: Discussionmentioning

confidence: 99%

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Association study of GRM7 polymorphisms and schizophrenia in the Chinese Han population

Niu

Huang

et al. 2015

Neuroscience Letters

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Section: Discussionmentioning

confidence: 99%

“…Additionally, a previous study pointed out that blocking GRM7 by the Venus Flytrap Domain (VFTD) inhibits synaptic plasticity, stress, and fear, anxiety in rodents [5].…”

Section: Discussionmentioning

confidence: 99%

Association study of GRM7 polymorphisms and schizophrenia in the Chinese Han population

Niu

Huang

et al. 2015

Neuroscience Letters

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“…GRM5 is an important presynaptic regulator of neurotransmission in the mammalian CNS [47]. GABRA5, the main inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Subtypes B and C Tat Differentially Impact Synaptic Plasticity Expression and Implicates HIV-Associated Neurocognitive Disorders§

Samikkannu¹,

Atluri²,

Arias³

et al. 2015

CHR

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Earlier studies have established that infection with HIV-1 subtypes (clades) might differentially influence the neuropathogenesis of HIV-1-associated neurocognitive dysfunction (HAND). HIV-1 Trans activator of transcription protein (Tat) is of considerable significance and plays a major role in the central nervous system (CNS) dysfunction. However, these HIV-1 clades exert diverse cellular effects that leads to neuropathogenic dysfunction has not been well established. We hypothesized that the HIV-1 clade B and clade C Tat proteins effect synaptic plasticity expression in neuroblastoma cells (SK-N-MC) by diverse methods, and accordingly modulates the development of HAND. In the present study, we have analyzed important and highly expressed 84 key human synaptic plasticity genes expression which differentially impact in clade B and clade C Tat treated SK-N-MC cells using RT2 Profile PCR Array human Synaptic Plasticity kit. Observed results demonstrate that out of 84 key synaptic plasticity genes, 36 and 25 synaptic genes were substantially (≥3 fold) up-regulated and 5 and 5 genes considerably (≥3 fold) down-regulated in clade B and clade C Tat treated cells, respectively, compared to the control SK-N-MC. We have also estimated the levels of glutamine and glutamate in HIV-1 clade B and C Tat exposed SK-N-MC cells compared to untreated cells. Our results indicate that levels of glutamate, glutamine and expression of synaptic plasticity genes were highly dysregulated by HIV-1 clade B Tat compared to clade C Tat in SK-N-MC cells. In summary, this study suggests that clade B Tat substantially potentiates neuronal toxicity and further dysregulated synaptic plasticity genes in SK-N-MC may contribute to the severe neuropathogenesis linked with HAND.

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“…ADX71743 attenuated L-AP4-induced Ca 2+ mobilization in cells that express rat (IC 50 = 63 nM) and human (IC 50 = 88 nM) mGluR7 [26]. The first mGluR7 orthosteric antagonist, XAP044 (7-hydroxy-3-[4-iodophenoxy]-4 H -chromen-4-one), was identified by Novartis [27]. XAP044 reduced L-AP4-induced GTPγS binding (IC 50 = 2.8–3.5 µM) but had no effect on AMN082-induced GTPγS binding in mGluR7-expressing cells [27].…”

Section: Mglur7 Ligandsmentioning

confidence: 99%

Metabotropic Glutamate Receptor 7 (mGluR7) as a Target for the Treatment of Psychostimulant Dependence

Li¹,

Markou

2015

CNSNDDT

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Although few medications have been approved by the U.S. Food and Drug Administration (FDA) to assist people to quit tobacco smoking, there are no FDA-approved medications to treat dependence on other psychostimulant drugs, such as cocaine. The motivation to maintain psychostimulant drug seeking and self-administration involves alterations in glutamatergic neurotransmission. Thus, medications that modulate glutamate transmission may be effective treatments for psychostimulant dependence. One presynaptic inhibitory glutamate receptor that critically regulates glutamate transmission is the metabotropic glutamate 7 receptor (mGluR7). This review summarizes nonhuman experimental animal data that indicate a critical role for mGluR7 in drug-taking and drug-seeking behaviors for the psychostimulants cocaine and nicotine. AMN082, the only commercially available allosteric receptor agonist, has been used to investigate the role of mGluR7 in psychostimulant dependence. Systemic administration or microinjection of AMN082 into brain sites within the mesocorticolimbic system decreased self-administration and reinstatement of both cocaine and nicotine seeking. In vivo microdialysis results indicated that a nucleus accumbens-ventral pallidum γ-aminobutyric acid-ergic mechanism may underlie AMN082-induced antagonism of the reinforcing effects of cocaine, whereas a glutamate mGlu2/3 receptor mechanism underlies the AMN082-induced blockade of cocaine seeking. These findings indicate an important role for mGluR7 in mesolimbic areas in modulating the reinforcing effects of psychostimulant drugs, such as nicotine and cocaine, and the conditioned behaviors associated with drugs of abuse. Thus, selective mGluR7 agonists or positive allosteric modulators may have the potential to treat psychostimulant dependence.

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Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior

Cited by 65 publications

References 61 publications

Association study of GRM7 polymorphisms and schizophrenia in the Chinese Han population

Association study of GRM7 polymorphisms and schizophrenia in the Chinese Han population

HIV-1 Subtypes B and C Tat Differentially Impact Synaptic Plasticity Expression and Implicates HIV-Associated Neurocognitive Disorders§

Metabotropic Glutamate Receptor 7 (mGluR7) as a Target for the Treatment of Psychostimulant Dependence

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Blocking Metabotropic Glutamate Receptor Subtype 7 (mGlu7) via the Venus Flytrap Domain (VFTD) Inhibits Amygdala Plasticity, Stress, and Anxiety-related Behavior

Cited by 65 publications

References 61 publications

Association study of GRM7 polymorphisms and schizophrenia in the Chinese Han population

Association study of GRM7 polymorphisms and schizophrenia in the Chinese Han population

HIV-1 Subtypes B and C Tat Differentially Impact Synaptic Plasticity Expression and Implicates HIV-Associated Neurocognitive Disorders&#167;

Metabotropic Glutamate Receptor 7 (mGluR7) as a Target for the Treatment of Psychostimulant Dependence

Contact Info

Product

Resources

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HIV-1 Subtypes B and C Tat Differentially Impact Synaptic Plasticity Expression and Implicates HIV-Associated Neurocognitive Disorders§