Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent work has demonstrated that specific patterns of synaptic stimulation can induce long-term depression (LTD) in area CA1 that depends on activation of metabotropic glutamate receptors (mGluRs) and rapid protein synthesis. Here we show that the same form of synaptic modification can be induced by brief application of the selective mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). DHPG-LTD 1) is a saturable form of synaptic plasticity, 2) requires mGluR5, 3) is mechanistically distinct from N-methyl-D-aspartate receptor (NMDAR)--dependent LTD, and 4) shares a common expression mechanism with protein synthesis-dependent LTD evoked using synaptic stimulation. DHPG-LTD should be useful for biochemical analysis of mGluR5- and protein synthesis-dependent synaptic modification.
 ...
PMID:Chemical induction of mGluR5- and protein synthesis--dependent long-term depression in hippocampal area CA1. 1143 13

Activation of metabotropic glutamate receptors (mGluRs), which are coupled to G proteins, has important roles in certain forms of synaptic plasticity including corticostriatal long-term depression (LTD). In the present study, extracellular field potential and whole cell voltage-clamp recording techniques were used to investigate the effect of mGluR antagonists with different subtype specificity on high-frequency stimulation (HFS)-induced LTD of synaptic transmission in the striatum of brain slices obtained from 15-to 25-day-old rats. Induction of LTD was prevented during exposure to the nonselective mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (500 microM). The group I mGluR-selective antagonists (S)-4-carboxy-phenylglycine (50 microM) and (RS)-1-aminoindan-1,5-dicarboxylic acid (100 microM) prevented induction of LTD when applied before and during HFS. The mGluR1-selective antagonist 7-(Hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (80 microM) also blocked LTD induction. Unexpectedly, the mGluR5-selective antagonist 2-methyl-6-(phenylethyl)-pyridine (10 microM) also prevented LTD induction. The group II mGluR antagonist LY307452 (10 microM) did not block LTD induction at corticostriatal synapses, but LY307452 was able to block transient synaptic depression induced by the group II agonist LY314593. None of the antagonists had any effect on basal synaptic transmission at the concentrations used, and mGluR antagonists did not reverse LTD when applied beginning 20 min after HFS. These results suggest that both group I mGluR subtypes contribute to the induction of LTD at corticostriatal synapses.
 ...
PMID:Activation of group I mGluRs is necessary for induction of long-term depression at striatal synapses. 1169 30

1. The aim of the study was to elucidate the mechanisms underlying the depressant effect of the group I/II metabotropic glutamate receptor (mGluR) agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) on parallel fibre (PF) to Purkinje cell (PC) synaptic transmission. Experiments were performed in rat cerebellar slices using the whole-cell patch-clamp technique and fluorometric measurements of presynaptic calcium variation 2. Analysis of short-term plasticity, fluctuation of EPSC amplitude and responses of PCs to exogenous glutamate showed that depression caused by 1S,3R-ACPD is presynaptic. 3. The effects of 1S,3R-ACPD were blocked and reproduced by group I mGluR antagonists and agonists, respectively. 4. These effects remained unchanged in mGluR5 knock-out mice and disappeared in mGluR1 knock-out mice. 5. 1S,3R-ACPD increased calcium concentration in PFs. This effect was abolished by AMPA/kainate (but not NMDA) receptor antagonists and mimicked by focally applied agonists of these receptors. Thus, it is not directly due to mGluRs but to presynaptic AMPA/kainate receptors indirectly activated by 1S,3R-ACPD. 6. Frequencies of spontaneous and evoked unitary EPSCs recorded in PCs were respectively increased and decreased by mGluR1 agonists. Similar results were obtained when mGluR1s were activated by tetanic stimulation of PFs. 7. Injecting 30 mM BAPTA into PCs blocked the effects of 1S,3R-ACPD on unitary EPSCs. 8. In conclusion, 1S,3R-ACPD reduces evoked release of glutamate from PFs. This effect is triggered by postsynaptic mGluR1s and thus implies that a retrograde messenger, probably glutamate, opens presynaptic AMPA/kainate receptors and consequently increases spontaneous release of glutamate from PF terminals and decreases evoked synaptic transmission.
 ...
PMID:Retrograde modulation of transmitter release by postsynaptic subtype 1 metabotropic glutamate receptors in the rat cerebellum. 1171 67

The aim of our study was to investigate the level of metabotropic glutamate receptors (mGluRs) in the brains of rats after chronic mild stress. Using Western blotting procedure we showed that the level of mGluR5 receptor protein was increased in CA1 and decreased in CA3 region of the hippocampus. Our results indicate that mGluR5 can possibly be engaged in the mechanism of depression.
 ...
PMID:Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in the rat hippocampus in an animal model of depression. 1198 42

1. The modulatory effects of mGlu receptors on NMDA-induced potential changes in spinal motoneurones were studied in vitro. 2. Selective activation of mGlu5 receptors by 10 microM (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG; EC(50)=280 +/- 24 microM) did not produce any change in the ventral root potential. However, the same concentration of CHPG (10 min perfusion) significantly attenuated the NMDA-induced ventral root depolarization (VRD). The effect persisted for 10 min after washout. NMDA-induced responses returned to control in 30 min. Brief co-application of CHPG and NMDA did not alter the NMDA-induced response indicating lack of direct receptor interaction. 3. The attenuating effect of CHPG on the NMDA-induced VRD was inhibited by the mGluR5 receptor antagonist, 2-methyl-6-phenyl-ethynylpyridine (MPEP). 4. In the presence of CGP56433A, a GABA(B) receptor antagonist, the NMDA-induced VRD was unchanged. However, NMDA-induced responses were potentiated after 10 min co-application of CHPG and CGP56433A. 5. (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group II mGlu receptor agonist did not attenuate the NMDA-induced response. 6. Under normal physiological conditions group I mGlu receptor agonists activate at least two populations of neurones: (1) GABA-ergic cells, which could release GABA and inhibit dorsal horn neurones, and (2) deep dorsal horn neurones/motoneurones which express NMDA receptors. Therefore, activation of mGlu5 receptors located on GABA-ergic interneurones could influence any direct potentiating interaction between mGlu5 and NMDA receptors in spinal cord and result in depression of the VRD. In the presence of a GABA(B) receptor antagonist, the direct synergistic interaction is unmasked. These data suggest that group I mGlu receptors provide a complex modulation of spinal synaptic processes.
 ...
PMID:Interaction of group I mGlu and NMDA receptor agonists within the dorsal horn of the spinal cord of the juvenile rat. 1201 Jul 73

3,5-dihydroxyphenylglycine (3,5-DHPG) was the first agonist shown to be group I metabotropic glutamate receptor selective with its agonist effects residing exclusively in the S-isomer. Some results suggest that (S)-3,5-DHPG may be a partial agonist of mGluR1a and mGluR5a in neurons and astrocytes. It has been reported that (S)-3,5-DHPG can, under certain conditions, interact with NMDA receptors. (S)-3,5-DHPG exerts different effects on second messengers in adult and neonatal tissues. It stimulates phosphoinositide hydrolysis in a dose-dependent manner in both the adult and neonate hippocampus, inhibits stimulated cAMP levels in the adult and enhances the cAMP in the neonate. It is an effective antagonist of mGluRs linked to phospholipase D (PLD) in the adult and an agonist in the neonate brain or astrocyte cultures. (S)-3,5-DHPG induces elevation of [Ca2+]i and regulates multiple subtypes of Ca2+ channels. This agonist of group I mGluRs may modulate neurotransmitters release, reflecting the diversity of mechanisms involved. Depending on the dose, (S)-3,5-DHPG enhances or decreases excitatory postsynaptic potentials (EPSPs) and under appropriate conditions it can induce long-term depression (LTD) and long-term potentiation (LTP). Some studies suggested a therapeutic role for (S)-3,5-DHPG in neuronal injury, regulation of intestinal motility and secretion, learning and memory processes and in cardiovascular system. (S)-3,5-DHPG may be useful as a cognitive enhancing agent in memory impairment associated with ischemia or hypoxia. Recent investigations suggested possible beneficial effects of (S)-3,5-DHPG in Alzheimer's disease.
 ...
PMID:(S)-3,5-DHPG: a review. 1207 May 29

Activation of group I metabotropic glutamate receptors (mGluRs) can induce acute depression of excitatory synaptic transmission and long-term depression (LTD) in area CA1 of the rat hippocampus. The underlying mechanisms for both forms of depression are unknown. By measuring presynaptic calcium transients, we show that a reduction in the stimulation-induced presynaptic calcium rise that triggers vesicular release causes the acute depression of transmission by group I mGluRs. In contrast, the mechanism underlying mGluR-induced LTD does not involve a persistent change in stimulation-induced calcium influx. However, analysis of paired-pulse facilitation experiments suggests a presynaptic location for expression of this form of LTD. Furthermore, we show that mGluR-induced LTD can be completely blocked by a specific mGluR5 antagonist, whereas mGluR1 antagonists strongly attenuate the acute depression of transmission. These results support the hypothesis that the acute depression of transmission caused by activation of group I mGluRs involves regulation of stimulation-induced presynaptic calcium transients, whereas mGluR-induced LTD involves a distinct presynaptic modulation downstream of calcium influx.
 ...
PMID:Modulation of presynaptic calcium transients by metabotropic glutamate receptor activation: a differential role in acute depression of synaptic transmission and long-term depression. 1217 86

The ability of activation of group I metabotropic glutamate receptor (mGluR) to induce depotentiation was investigated at Schaffer collateral-CA1 synapses of rat hippocampal slices. Brief bath application (5 min) of group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) (10 microm) induced a long-term depression of synaptic transmission or depotentiation (DEP) of previously established long-term potentiation (LTP), which was independent of NMDA or A(1) adenosine receptor activation. This DHPG-DEP was observed when DHPG was delivered 3 min after LTP induction. However, when DHPG was applied at 10 or 30 min after LTP induction, significantly less depotentiation was found. DHPG-DEP (1) is reversible and has the ability to unsaturate LTP, (2) is synapse specific, (3) does not require concurrent synaptic stimulation, (4) is mechanistically distinct from NMDA receptor-dependent depotentiation, (5) requires mGluR5 activation, (6) requires rapamycin-sensitive mRNA translation signaling, (7) does not require phospholipase C or protein phosphatase activation, and (8) is not associated with a change in paired-pulse (PP) facilitation. In addition, the ability of DHPG to reverse LTP was mimicked by a long train of low-frequency (1 Hz/15 min) PP stimulation. Moreover, the expression of DHPG-DEP is associated with a reduction in the increase of the surface expression of AMPA receptors seen with LTP. These results suggest that the activation of mGluR5 and in turn the triggering of a protein synthesis-dependent internalization of synaptic AMPA receptors may contribute to the DHPG-DEP in the CA1 region of the hippocampus.
 ...
PMID:The group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine induces a novel form of depotentiation in the CA1 region of the hippocampus. 1238 90

Metabotropic glutamate receptors (mGluRs) have been demonstrated to play a role in synaptic plasticity. It has been recently shown that mGluR1 is involved in corticostriatal long-term depression, by means of pharmacological approach and by using mGluR1-knockout mice. Here, we report that both mGluR1 and mGluR5 are involved in corticostriatal long-term potentiation (LTP). In particular, the mGluR1 antagonist LY 367385, as well as the mGluR5 antagonist MPEP, reduce LTP amplitude. Moreover, blockade of both mGluR1 and mGluR5 by LY 367385 and MPEP co-administration fully suppresses LTP. Accordingly, group II and group III mGluRs antagonists fail to affect LTP induction. Interestingly, LTP amplitude is also significantly reduced in both mGluR1- and mGluR5-knockout mice. The differential function of mGluR1 and mGluR5 in corticostriatal synaptic plasticity may play a role in the modulation of the motor activity mediated by the basal ganglia, thus providing a substrate for the pharmacological treatment of motor disorders involving the striatum.
 ...
PMID:Corticostriatal LTP requires combined mGluR1 and mGluR5 activation. 1255 17

The effects of high frequency stimulation (HFS) of the primary vestibular afferents on synaptic transmission in the ventral part of the medial vestibular nuclei (vMVN) were studied during postnatal development and compared with the changes in the expression of the group I metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and mGluR5. During the first stages of development, HFS always induced a mGluR5- and GABAA-dependent long-term depression (LTD) which did not require NMDA receptor and mGluR1 activation. The probability of inducing LTD decreased progressively throughout the development and it was zero at about the end of the second postnatal week. Conversely, long-term potentiation (LTP) appeared at the beginning of the second week and its occurrence increased to reach the adult value at the end of the third week. Of interest, the sudden change in the LTP frequency occurred at the time of eye opening, about the end of the second postnatal week. LTP depended on NMDA receptor and mGluR1 activation. In parallel with the modifications in synaptic plasticity, we observed that the expression patterns and localizations of mGluR5 and mGluR1 in the medial vestibular nuclei (MVN) changed during postnatal development. At the earlier stages the mGluR1 expression was minimal, then increased progressively. In contrast, mGluR5 expression was initially high, then decreased. While mGluR1 was exclusively localized in neuronal compartments and concentrated at the postsynaptic sites at all stages observed, mGluR5 was found mainly in neuronal compartments at immature stages, then preferentially in glial compartments at mature stages. These results provide the first evidence for a progressive change from LTD to LTP accompanied by a distinct maturation expression of mGluR1 and mGluR5 during the development of the MVN.
 ...
PMID:Developmental shift from long-term depression to long-term potentiation in the rat medial vestibular nuclei: role of group I metabotropic glutamate receptors. 1297 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>