Kooperativer Bibliotheksverbund

Berlin Brandenburg

and
and

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Receptors, Metabotropic Glutamate  (101)
Type of Medium
Language
Year
  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 19 March 2013, Vol.110(12), pp.4804-9
    Description: Epigenetic mechanisms are involved in the pathophysiology of depressive disorders and are unique potential targets for therapeutic intervention. The acetylating agent L-acetylcarnitine (LAC), a well-tolerated drug, behaves as an antidepressant by the epigenetic regulation of type 2 metabotropic glutamate (mGlu2) receptors. It caused a rapid and long-lasting antidepressant effect in Flinders Sensitive Line rats and in mice exposed to chronic unpredictable stress, which, respectively, model genetic and environmentally induced depression. In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-ĸB-p65 subunit, thereby enhancing the transcription of Grm2 gene encoding for the mGlu2 receptor in hippocampus and prefrontal cortex. Importantly, LAC reduced the immobility time in the forced swim test and increased sucrose preference as early as 3 d of treatment, whereas 14 d of treatment were needed for the antidepressant effect of chlorimipramine. Moreover, there was no tolerance to the action of LAC, and the antidepressant effect was still seen 2 wk after drug withdrawal. Conversely, NF-ĸB inhibition prevented the increase in mGlu2 expression induced by LAC, whereas the use of a histone deacetylase inhibitor supported the epigenetic control of mGlu2 expression. Finally, LAC had no effect on mGlu2 knockout mice exposed to chronic unpredictable stress, and a single injection of the mGlu2/3 receptor antagonist LY341495 partially blocked LAC action. The rapid and long-lasting antidepressant action of LAC strongly suggests a unique approach to examine the epigenetic hypothesis of depressive disorders in humans, paving the way for more efficient antidepressants with faster onset of action.
    Keywords: Acetylcarnitine -- Pharmacology ; Antidepressive Agents -- Pharmacology ; Epigenesis, Genetic -- Drug Effects ; Hippocampus -- Metabolism ; Nerve Tissue Proteins -- Biosynthesis ; Prefrontal Cortex -- Metabolism ; Receptors, Metabotropic Glutamate -- Biosynthesis
    ISSN: 00278424
    E-ISSN: 1091-6490
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Neuropsychopharmacology, 2011, Vol.37(4), p.929
    Description: Prenatal exposure to restraint stress causes long-lasting changes in neuroplasticity that likely reflect pathological modifications triggered by early-life stress. We found that the offspring of dams exposed to repeated episodes of restraint stress during pregnancy (here named 'prenatal restraint stress mice' or 'PRS mice') developed a schizophrenia-like phenotype, characterized by a decreased expression of brain-derived neurotrophic factor and glutamic acid decarboxylase 67, an increased expression of type-1 DNA methyl transferase (DNMT1) in the frontal cortex, and a deficit in social interaction, locomotor activity, and prepulse inhibition. PRS mice also showed a marked decrease in metabotropic glutamate 2 (mGlu2) and mGlu3 receptor mRNA and protein levels in the frontal cortex, which was manifested at birth and persisted in adult life. This decrease was associated with an increased binding of DNMT1 to CpG-rich regions of mGlu2 and mGlu3 receptor promoters and an increased binding of MeCP2 to the mGlu2 receptor promoter. Systemic treatment with the selective mGlu2/3 receptor agonist LY379268 (0.5 mg/kg, i.p., twice daily for 5 days), corrected all the biochemical and behavioral abnormalities shown in PRS mice. Our data show for the first time that PRS induces a schizophrenia-like phenotype in mice, and suggest that epigenetic changes in mGlu2 and mGlu3 receptors lie at the core of the pathological programming induced by early-life stress.
    Keywords: Medicine ; Pharmacy, Therapeutics, & Pharmacology ; Anatomy & Physiology;
    ISSN: 0893-133X
    E-ISSN: 1740634X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Psychopharmacology, 2011, Vol.217(3), pp.301-313
    Description: Byline: Sara Morley-Fletcher (1), Jerome Mairesse (1), Amelie Soumier (2), Mounira Banasr (2), Francesca Fagioli (3), Cecilia Gabriel (4), Elisabeth Mocaer (4), Annie Daszuta (2), Bruce McEwen (5), Ferdinando Nicoletti (1,6,7), Stefania Maccari (1) Keywords: Agomelatine; Prenatal stress; Adult neurogenesis; Ventral hippocampus; Fluoxetine; Phospho-CREB; Metabotropic glutamate receptors Abstract: Rationale and objectives The rat model of prenatal restraint stress (PRS) replicates factors that are implicated in the etiology of anxious/depressive disorders. We used this model to test the therapeutic efficacy of agomelatine, a novel antidepressant that behaves as a mixed MT1/MT2 melatonin receptor agonist/5-HT.sub.2c serotonin receptor antagonist. Results Adult PRS rats showed behavioral, cellular, and biochemical abnormalities that were consistent with an anxious/depressive phenotype. These included an increased immobility in the forced swim test, an anxiety-like behavior in the elevated plus maze, reduced hippocampal levels of phosphorylated cAMP-responsive element binding protein (p-CREB), reduced hippocampal levels of mGlu2/3 and mGlu5 metabotropic glutamate receptors, and reduced neurogenesis in the ventral hippocampus, the specific portion of the hippocampus that encodes memories related to stress and emotions. All of these changes were reversed by a 3- or 6-week treatment with agomelatine (40--50 mg/kg, i.p., once a day). Remarkably, agomelatine had no effect in age-matched control rats, thereby behaving as a "disease-dependent" drug. Conclusions These data indicate that agomelatine did not act on individual symptoms but corrected all aspects of the pathological epigenetic programming triggered by PRS. Our findings strongly support the antidepressant activity of agomelatine and suggest that the drug impacts mechanisms that lie at the core of anxious/depressive disorders. Author Affiliation: (1) Neuroplasticity Team, UMR 8576 CNRS Structural and Functional Glycobiology Unit, University Lille North of France (USTL), 59655, Villeneuve d'Ascq, France (2) IC2N, IBDLM, UMR6216, CNRS, Marseille, France (3) Azienda Sanitaria Locale, RM.E. Unita Operativa Complessa Adolescent, Rome, Italy (4) Institut de Recherches Internationales Servier, Courbevoie, France (5) Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, USA (6) Department of Human Physiology and Pharmacology, Sapienza University, Rome, Italy (7) I.N.M. Neuromed, Pozzilli, Italy Article History: Registration Date: 24/03/2011 Received Date: 10/01/2011 Accepted Date: 23/03/2011 Online Date: 19/04/2011 Article note: S. Morley-Fletcher and J. Mairesse contributed equally to this work.
    Keywords: Agomelatine ; Prenatal stress ; Adult neurogenesis ; Ventral hippocampus ; Fluoxetine ; Phospho-CREB ; Metabotropic glutamate receptors
    ISSN: 0033-3158
    E-ISSN: 1432-2072
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    In: Epilepsia, July 2015, Vol.56(7), pp.1141-1151
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/epi.13024/abstract Byline: Valerio D'Amore, Constanze Randow, Ferdinando Nicoletti, Richard Teke Ngomba, Gilles Luijtelaar Keywords: Glutamate; GABA ; Absence epilepsy; WAG/Rij rats; mGlu PAM Summary Objective Glutamate and [gamma]-aminobutyric acid (GABA) are the key neurotransmitter systems in the cortical-thalamocortical network, involved in normal and pathologic oscillations such as spike-wave discharges (SWDs), which characterize different forms of absence epilepsy. Metabotropic glutamate (mGlu) and GABA receptors are widely expressed within this network. Herein, we examined the effects of two selective positive allosteric modulators (PAMs) of mGlu1 and mGlu5 receptors, the GABA reuptake inhibitor, tiagabine, and their interaction in the somatosensory cortex and thalamus on SWDs in WAG/Rij rats. Methods Male WAG/Rij rats were equipped with bilateral cannulas in the somatosensory cortex (S1po) or the ventrobasal (VB) thalamic nuclei, and with cortical electroencephalography (EEG) electrodes. Rats received a single dose of the mGlu1 receptor PAM, RO0711401, or the mGlu5 receptor PAM, VU0360172, various doses of tiagabine, or VU0360172 combined with tiagabine. Results Both PAMs suppressed SWDs regardless of the site of injection. Tiagabine enhanced SWDs when injected into the thalamus, but, unexpectedly, suppressed SWDs in a dose-dependent manner when injected into the cortex. Intracortical co-injection of VU0360172 and tiagabine produced slightly larger effects as compared to either VU0360172 or tiagabine alone. Intrathalamic co-injections of VU0360172 and subthreshold doses of tiagabine caused an antiabsence effect similar to that exhibited by VU0360172 alone in the first 10 min. At 30 min, however, the antiabsence effect of VU0360172 was prevented by subthreshold doses of tiagabine, and the combination produced a paradoxical proabsence effect at 40 and 50 min. Significance These data (1) show that mGlu1 and mGlu5 receptor PAMs reduce absence seizures acting at both thalamic and cortical levels; (2) demonstrate for the first time that tiagabine, despite its established absence-enhancing effect, reduces SWDs when injected into the somatosensory cortex; and (3) indicate that the efficacy of VU0360172 in the thalamus may be critically affected by the availability of (extra)synaptic GABA. CAPTION(S): Data S1. Surgery and EEG Recordings.
    Keywords: Glutamate ; Gaba ; Absence Epilepsy ; Wag /Rij Rats ; Mg Lu Pam
    ISSN: 0013-9580
    E-ISSN: 1528-1167
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Epilepsia, July 2011, Vol.52(7), pp.1211-22
    Description: Metabotropic glutamate (mGlu) receptors are positioned at synapses of the thalamocortical network that underlie the development of spike-and-wave discharges (SWDs) associated with absence epilepsy. The modulatory role of individual mGlu receptor subtypes on excitatory and inhibitory synaptic transmission in the cortico-thalamo-cortical circuitry makes subtype-selective mGlu receptor ligands potential candidates as novel antiabsence drugs. Some of these compounds are under clinical development for the treatment of numerous neurologic and psychiatric disorders, and might be soon available for clinical studies in patients with absence seizures refractory to conventional medications. Herein we review the growing evidence that links mGlu receptors to the pathophysiology of pathologic SWDs moving from the anatomic localization and function of distinct mGlu receptor subtypes in the cortico-thalamo-cortical network to in vivo studies in mouse and rat models of absence epilepsy.
    Keywords: Anticonvulsants -- Pharmacology ; Cerebral Cortex -- Physiology ; Epilepsy, Absence -- Drug Therapy ; Receptors, Metabotropic Glutamate -- Physiology ; Thalamus -- Physiology
    ISSN: 00139580
    E-ISSN: 1528-1167
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Current Opinion in Pharmacology, February 2012, Vol.12(1), pp.28-34
    Description: ► Chronic pain is a severe and debilitating condition with a very high impact in the general population. ► mGlu receptors have been involved in the modulation of many forms of chronic pain, including inflammatory and neuropathic pain. ► Recent findings coming from the use of subtype-selective mGlu receptor ligands, together with the knockout strategy, have shed more light about the role of specific mGlu receptor subtypes in the modulation of pain processing. ► Pharmacological and epigenetic approaches to manage chronic pain through mGlu receptors are discussed here. Over the past two decades metabotropic glutamate (mGlu) receptor ligands have been investigated for their potential therapeutic effects in different disorders of the central nervous system (CNS), including anxiety, depression, schizophrenia, and neurodegenerative diseases. In addition, it has been widely demonstrated that mGlu receptors are able to modulate pain transmission both in inflammatory and neuropathic pain models. A large number of preclinical studies combining the use of selective ligands with the knockout strategy have revealed more details about the role of the different mGlu receptor subtypes in the modulation of pain information. This review will address the role of mGlu receptors in pain sensitivity focusing on different strategies to achieve pain control by targeting specific mGlu receptor subtypes. Specifically, pharmacological interventions aimed at inhibiting group I mGlu receptor-mediated signaling and/or potentiating groups II and III mGlu receptor signaling together with an epigenetic approach leading to an increased expression of mGlu2 receptors will be discussed.
    Keywords: Pharmacy, Therapeutics, & Pharmacology
    ISSN: 1471-4892
    E-ISSN: 1471-4973
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Endocrinology, December 2012, Vol.153(12), pp.5940-8
    Description: Pretreatment with 10 nm 17β-estradiol (17βE2) or 100 μm of the metabotropic glutamate 1 receptor (mGlu1R) agonist, dihydroxyphenylglycine (DHPG), protected neurons against N-methyl-d-aspartate (NMDA) toxicity. This effect was sensitive to blockade of both estrogen receptors and mGlu1R by their respective antagonists. In contrast, 17βE2 and/or DHPG, added after a low-concentration NMDA pulse (45 μm), produced an opposite effect, i.e. an exacerbation of NMDA toxicity. Again this effect was prevented by both receptor antagonists. In support of an interaction of estrogen receptors and mGlu1R in mediating a neurotoxic response, exacerbation of NMDA toxicity by 17βE2 disappeared when cultures were treated with DHPG prior to NMDA challenge, and conversely, potentiation of NMDA-induced cell death by DHPG was prevented by pretreatment with 17βE2. Addition of calpain III inhibitor (10 μm), 2 h before NMDA, prevented the increased damage induced by the two agonists, an affect that can be secondary to cleavage of mGlu1R by calpain. Accordingly, NMDA stimulation reduced expression of the full-length (140 kDa) mGluR1, an effect partially reversed by calpain inhibitor. Finally, in the presence of NMDA, the ability of 17βE2 to stimulate phosphorylation of AKT and ERK was impaired. Pretreatment with calpain inhibitor prevented the reduction of phosphorylated ERK but had no significant effect on phosphorylated AKT. Accordingly, the inhibition of ERK signaling by U0126 (1 μm) counteracted the effect of calpain inhibition on 17βE2-induced exacerbation of NMDA toxicity. The present data confirm the dual role of estrogens in neurotoxicity/neuroprotection and highlight the role of the timing of exposure to estrogens.
    Keywords: Cell Death -- Drug Effects ; Estradiol -- Metabolism ; N-Methylaspartate -- Pharmacology ; Neurons -- Metabolism ; Receptors, Metabotropic Glutamate -- Metabolism
    ISSN: 00137227
    E-ISSN: 1945-7170
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    In: Nature Medicine, 2010, Vol.16(8), p.897
    Description: High amounts of glutamate are found in the brains of people with multiple sclerosis, an inflammatory disease marked by progressive demyelination. Glutamate might affect neuroinflammation via effects on immune cells. Knockout mice lacking metabotropic glutamate receptor-4 (mGluR4) were markedly vulnerable to experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis) and developed responses dominated by interleukin-17-producing T helper ([T.sub.H]17) cells. In dendritic cells (DCs) from those mice, defective mGluR4 signaling--which would normally decrease intracellular cAMP formation--biased [T.sub.H] cell commitment to the [T.sub.H]17 phenotype. In wild-type mice, mGluR4 was constitutively expressed in all peripheral DCs, and this expression increased after cell activation. Treatment of wild-type mice with a selective mGluR4 enhancer increased EAE resistance via regulatory T ([T.sub.reg]) cells. The high amounts of glutamate in neuroinflammation might reflect a counterregulatory mechanism that is protective in nature and might be harnessed therapeutically for restricting immunopathology in multiple sclerosis.
    Keywords: Multiple Sclerosis -- Risk Factors ; Multiple Sclerosis -- Care And Treatment ; Multiple Sclerosis -- Research ; Neurotransmitter Receptors -- Physiological Aspects ; Neurotransmitter Receptors -- Research ; T Cells -- Physiological Aspects ; T Cells -- Research;
    ISSN: 1078-8956
    E-ISSN: 1546170X
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Language: English
    In: Neuron, 02 October 2013, Vol.80(1), pp.72-79
    Description: A novel experience induces the gene as well as plasticity of CA1 neural networks. To understand how these are linked, we briefly exposed GFP reporter mice of transcription to a novel environment. Excitatory synaptic function of CA1 neurons with recent in vivo induction ( GFP+) was similar to neighboring noninduced neurons. However, in response to group 1 metabotropic glutamate receptor (mGluR) activation, GFP+ neurons preferentially displayed long-term synaptic depression (mGluR-LTD) and robust increases in dendritic Arc protein. mGluR-LTD in GFP+ neurons required rapid protein synthesis and , suggesting that dendritic translation of Arc underlies the priming of mGluR-LTD. In support of this idea, novelty exposure increased messenger RNA in CA1 dendrites and promoted mGluR-induced translation of Arc in hippocampal synaptoneurosomes. Repeated experience suppressed synaptic transmission onto GFP+ neurons and occluded mGluR-LTD ex vivo. mGluR-LTD priming in neurons with similar activation history may contribute to encoding a novel environment. The consequence of experience-induced Arc gene on synaptic function is unknown. Jakkamsetti et al. find that novelty-induced Arc primes CA1 neurons for mGluR-dependent long-term synaptic depression through rapid translation of dendritic Arc mRNA, which may contribute to encoding of a salient experience.
    Keywords: Biology ; Anatomy & Physiology
    ISSN: 0896-6273
    E-ISSN: 1097-4199
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Language: English
    In: Neuroscience, 05 November 2017, Vol.363, pp.142-149
    Description: Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced retinal degeneration, glaucoma, and age-related macular degeneration. In all these disorders excitotoxicity is a prominent component of neuronal damage, but clinical data discourage the development of NMDA receptor antagonists as neuroprotectants. Here, we show that activation of mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration of RGCs. Mice at postnatal day 9 were challenged with a toxic dose of monosodium glutamate (MSG, 3 g/kg), which caused the death of 〉70% of Brn-3a RGCs. Systemic administration of the mGlu1 receptor negative allosteric modulator (NAM), JNJ16259685 (2.5 mg/kg, s.c.), was largely protective against MSG-induced RGC death. This treatment did not cause changes in motor behavior in the pups. We also injected MSG to mice, which lack mGlu1 receptors because of a recessive mutation of the gene encoding the mGlu1 receptor. MSG did not cause retinal degeneration in mice, whereas it retained its toxic activity in their wild-type littermates. These findings demonstrate that mGlu1 receptors play a key role in excitotoxic degeneration of RGCs, and encourage the study of mGlu1 receptor NAMs in models of retinal neurodegeneration.
    Keywords: Retinal Ganglion Cells ; Mglu1 Receptors ; Monosodium Glutamate ; Jnj16258695 ; Crv4 Mice ; Anatomy & Physiology
    ISSN: 0306-4522
    E-ISSN: 1873-7544
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages