Distribution of metabotropic glutamate receptor 7 messenger RNA in the developing and adult rat brain

doi:10.1016/0306-4522(95)00244-D

Neuroscience

Volume 69, Issue 1, November 1995, Pages 167-176

https://doi.org/10.1016/0306-4522(95)00244-D Get rights and content

Abstract

The large number of metabotropic glutamate receptor subtypes suggests diverse roles in brain function, although specific distribution patterns can give clues to subtype-specific functions [Hayashi Y. et al. (1993) Nature366, 687–690; Nakajima Y. et al. (1993) J. biol. Chem.268, 11868–11873; Nomura A. et al. (1994) Cell77, 361–369; Ohishi H. et al. (1993) Neuroscience53, 1009–1018]. The metabotropic glutamate receptor mGluR7 is sensitive to the agonistl-2-amino-4-phosphonobutyric acid, a presynaptic inhibitor of neurotransmitter release. We examined the anatomic distribution of mGluR7 messenger RNA expression by in situ hybridization in the developing and adult rat central nervous system. Our results demonstrate that mGluR7 messenger RNA is among the most widely distributed of metabotropic glutamate receptors in both the developing and adult rat nervous system and that mGluR7 messenger RNA is expressed in most neuronal groups known to respond tol-2-amino-4-phosphonobutyric acid, including mitral cells of the olfactory bulb, granule cells of the dentate gyrus and neurons of the entorhinal cortex and dorsal root ganglion. mGluR7 exhibits preferential expression in sensory afferent pathways and is highly represented in the periventricular zone of the hypothalamus, the latter implying a modulatory role for mGluR7 in neuroendocrine pathways. Most strikingly, the majority of neurons at all levels of olfactory circuitry are among the areas of highest mGluR7 messenger RNA content.

The anatomic distribution of mGluR7 messenger RNA suggests that mGluR7 activation may participate in the processing of hippocampal, sensory and olfactory information.

References (45)

AbeT. et al.
Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca²⁺ signal transduction
J. biol. Chem.
(1992)
CollinsG.
Some effects of excitatory amino acid receptor antagonists on synaptic transmission in the rat olfactory cortex slice
Brain Res.
(1982)
CollinsG.G. et al.
The pharmacology of excitatory transmission in the rat olfactory cortex slice
Neuropharmacology
(1988)
DaviesJ. et al.
Actions ofd andl forms of 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate in the cat spinal cord
Brain Res.
(1982)
EvansR.H.
Pharmacology of amino acid receptors in vertebrate primary afferent nerve fibres
Gen. Pharmac.
(1986)
GanongA.H. et al.
Acidic amino acid antagonists of lateral perforant path synaptic transmission: agonist-antagonist interactions in the dentate gyrus
Neurosci. Lett.
(1982)
GraybielA.M.
Neurotransmitters and neuromodulators in the basal ganglia
Trends Neurosci.
(1990)
HaberlyL.B. et al.
Olfactory cortex: model circuit for study of associative memory?
Trends Neurosci.
(1989)
HasselmoM.E. et al.
Selective suppression of afferent but not intrinsic fiber synaptic transmission by 2-amino-4-phosphonobutyric acid (AP4) in piriform cortex
Brain Res.
(1991)
HearnT.J. et al.
Antagonism of lateral olfactory tract synaptic potentials in rat prepyriform cortex slices
Brain Res.
(1986)

KabaH. et al.

The effect of microinfusions of drugs into the accessory olfactory bulb on the olfactory block to pregnancy

Neuroscience

(1988)

KoernerJ.F. et al.

l-2-Amino-phosphonobutyric acid selectively inhibits perforant path synapses from lateral entorhinal cortex

Brain Res.

(1981)

LanthornT.H. et al.

2-Amino-4-phosphonobutyrate selectively blocks mossy fiber—CA3 responses in guinea pig but not rat hippocampus

Brain Res.

(1984)

LeonM.

Plasticity of olfactory output circuits related to early olfactory learning

Trends Neurosci.

(1987)

MayerM. et al.

The physiology of excitatory amino acids in the vertebrate central nervous system

Prog. Neurobiol.

(1987)

NakajimaY. et al.

Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity forl-2-amino-4-phosphonobutyrate

J. biol. Chem.

(1993)

NakanishiS.

Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity

Neuron

(1994)

NomuraA. et al.

Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells

Cell

(1994)

OhishiH. et al.

Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat

Neuroscience

(1993)

OkamotoN. et al.

Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction

J. biol. Chem.

(1994)

SaugstadJ.A. et al.

l-2-Amino-3-phosphonopropionic acid competitively antagonizes metabotropic glutamate receptors 1α and 5 in Xenopus oocytes

Eur. J. Pharmac.

(1995)

SchoeppD.D. et al.

Metabotropic glutamate receptors in brain function and pathology

Trends pharmac. Sci.

(1993)

Cited by (136)

Targeting mGluR group III for the treatment of neurodegenerative diseases
2023, Biomedicine and Pharmacotherapy
Glutamate, an excitatory neurotransmitter, is essential for neuronal function, and it acts on ionotropic or metabotropic glutamate receptors (mGluRs). A disturbance in glutamatergic signaling is a hallmark of many neurodegenerative diseases. Developing disease-modifying treatments for neurodegenerative diseases targeting glutamate receptors is a promising avenue. The understudied group III mGluR 4, 6–8 are commonly found in the presynaptic membrane, and their activation inhibits glutamate release. Thus, targeted mGluRs therapies could aid in treating neurodegenerative diseases. This review describes group III mGluRs and their pharmacological ligands in the context of amyotrophic lateral sclerosis, Parkinson’s, Alzheimer’s, and Huntington's diseases. Attempts to evaluate the efficacy of these drugs in clinical trials are also discussed. Despite a growing list of group III mGluR-specific pharmacological ligands, research on the use of these drugs in neurodegenerative diseases is limited, except for Parkinson’s disease. Future efforts should focus on delineating the contribution of group III mGluR to neurodegeneration and developing novel ligands with superior efficacy and a favorable side effect profile for the treatment of neurodegenerative diseases.
Membrane trafficking and positioning of mGluRs at presynaptic and postsynaptic sites of excitatory synapses
2021, Neuropharmacology
The plethora of functions of glutamate in the brain are mediated by the complementary actions of ionotropic and metabotropic glutamate receptors (mGluRs). The ionotropic glutamate receptors carry most of the fast excitatory transmission, while mGluRs modulate transmission on longer timescales by triggering multiple intracellular signaling pathways. As such, mGluRs mediate critical aspects of synaptic transmission and plasticity. Interestingly, at synapses, mGluRs operate at both sides of the cleft, and thus bidirectionally exert the effects of glutamate. At postsynaptic sites, group I mGluRs act to modulate excitability and plasticity. At presynaptic sites, group II and III mGluRs act as auto-receptors, modulating release properties in an activity-dependent manner. Thus, synaptic mGluRs are essential signal integrators that functionally couple presynaptic and postsynaptic mechanisms of transmission and plasticity. Understanding how these receptors reach the membrane and are positioned relative to the presynaptic glutamate release site are therefore important aspects of synapse biology. In this review, we will discuss the currently known mechanisms underlying the trafficking and positioning of mGluRs at and around synapses, and how these mechanisms contribute to synaptic functioning. We will highlight outstanding questions and present an outlook on how recent technological developments will move this exciting research field forward.
This article is part of the Neuropharmacology Special Issue on ‘Glutamate Receptors – mGluRs’.
New evidences for a role of mGluR7 in astrocyte survival: Possible implications for neuroprotection
2018, Neuropharmacology
A specific activation of metabotropic glutamate receptor 7 (mGluR7) has been shown to be neuroprotective in various models of neuronal cell damage, however, its role in glia cell survival has not been studied, yet. Thus, we performed comparative experiments estimating protective effects of the mGluR7 allosteric agonist AMN082 in glia, neuronal and neuronal-glia cell cultures against various harmful stimuli. First, the transcript levels of mGluR7 and other subtypes of group II and III mGluRs in cortical neuronal, neuronal-glia and glia cell cultures have been measured by qPCR method. Next, we demonstrated that AMN082 with similar efficiency attenuated the glia cell damage evoked by staurosporine (St) and doxorubicin (Dox). The AMN082-mediated glioprotection was mGluR7-dependent and associated with decreased DNA fragmentation without involvement of caspase-3 inhibition. Moreover, the inhibitors of PI3K/Akt and MAPK/ERK1/2 pathways blocked the protective effect of AMN082. In neuronal and neuronal-glia cell cultures in the model of glutamate (Glu)- but not St-evoked cell damage, we showed a significant glia contribution to mGluR7-mediated neuroprotection. Finally, by using glia and neuronal cells derived from mGluR7+/+ and mGluR7−/− mice we demonstrated a higher cell-damaging effect of St and Dox in mGluR7-deficient glia but not in neurons (cerebellar granule cells). Our present data showed for the first time a glioprotective potential of AMN082 underlain by mechanisms involving the activation of PI3K/Akt and MAPK/ERK1/2 pathways and pro-survival role of mGluR7 in glia cells. These findings together with the confirmed neuroprotective properties of AMN082 justify further research on mGluR7-targeted therapies for various CNS disorders.
Effect of Novel Allosteric Modulators of Metabotropic Glutamate Receptors on Drug Self-administration and Relapse: A Review of Preclinical Studies and Their Clinical Implications
2018, Biological Psychiatry
Results from preclinical rodent studies during the last 20 years implicated glutamate neurotransmission in different brain regions in drug self-administration and rodent models of relapse. These results, along with evidence for drug-induced neuroadaptations in glutamatergic neurons and receptors, suggested that addiction might be treatable by medications that inhibit glutamatergic responses to drugs of abuse, drug-associated cues, and stressors. This idea is supported by findings in rodent and primate models that drug self-administration and relapse are reduced by systemic injections of antagonists of ionotropic glutamate receptors or metabotropic glutamate receptors (mGluRs) or orthosteric agonists of mGluR2/3. However, these compounds have not advanced to clinical use because of potential side effects and other factors. This state of affairs has led to the development of positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs) of mGluRs. PAMs and NAMs of mGluRs, either of which can inhibit evoked glutamate release, may be suitable for testing in humans. We reviewed results from recent studies of systemically injected PAMs and NAMs of mGluRs in rodents and monkeys, focusing on whether they reduce drug self-administration, reinstatement of drug seeking, and incubation of drug craving. We also review results from rat studies in which PAMs or NAMs of mGluRs were injected intracranially to reduce drug self-administration and reinstatement. We conclude that PAMs and NAMs of mGluRs should be considered for clinical trials.
Off-target potential of AMN082 on sleep EEG and related physiological variables: Evidence from mGluR7 (-/-) mice
2016, Behavioural Brain Research
The metabotropic glutamate receptor type 7 (mGluR7), a most abundant presynaptic G protein-coupled receptor in the brain provides an attractive mechanism to fast fine-tune abnormal excitatory neurotransmission and synaptic plasticity associated with emotional and cognitive impairments in neuropsychiatric and neurodegenerative disorders. Preclinical studies using AMN082, the mGluR7 allosteric agonist, produced conflicting results, so that results of further in-vivo studies are needed. Here, we investigated effects of subcutaneous administration at the lights onset of AMN082 on sleep-wake architecture and spectral contents in rats. In an attempt to solve the reported mixed results, we estimated the specific functional effects in mGluR7 (−/−) mice and their wild type (WT) littermates. In rats, AMN082 (2.5 mg/kg) elicited a primary waking effect over the first 2 h post-administration by consistent increases in the number of waking bouts and transitions from sleep states towards wakefulness. In mice, baseline recordings over 72 h showed comparable spontaneous sleep-wake cycle in mGluR7 (−/−) mice and their WT littermates, suggesting that mGluR7 is not involved in the regulation of vigilance states. Remarkably, cortical arousal properties of AMN082 were confirmed in WT mice, and occurred concomitantly with a marked decrease in body temperature, likely dissociated from locomotor activity. Surprisingly, the wake arousal and hypothermia effects of AMN082 were also observed in mGluR7 (−/−) mice. AMN082 significantly attenuated the slow wave activity during sleep and had no effect on waking EEG power in the 4–50 Hz range. The present findings in rats do not lend support to proposed somnogenic effects of AMN082, while comparable responses in WT and mGluR7 (−/−) mice provide further evidence of an off-target action of AMN082 that contributes to its waking properties.
CART in the brain of vertebrates: Circuits, functions and evolution
2014, Peptides
Cocaine- and amphetamine-regulated transcript peptide (CART) with its wide distribution in the brain of mammals has been the focus of considerable research in recent years. Last two decades have witnessed a steady rise in the information on the genes that encode this neuropeptide and regulation of its transcription and translation. CART is highly enriched in the hypothalamic nuclei and its relevance to energy homeostasis and neuroendocrine control has been understood in great details. However, the occurrence of this peptide in a range of diverse circuitries for sensory, motor, vegetative, limbic and higher cortical areas has been confounding. Evidence that CART peptide may have role in addiction, pain, reward, learning and memory, cognition, sleep, reproduction and development, modulation of behavior and regulation of autonomic nervous system are accumulating, but an integration has been missing. A steady stream of papers has been pointing at the therapeutic potentials of CART. The current review is an attempt at piecing together the fragments of available information, and seeks meaning out of the CART elements in their anatomical niche. We try to put together the CART containing neuronal circuitries that have been conclusively demonstrated as well as those which have been proposed, but need confirmation. With a view to finding out the evolutionary antecedents, we visit the CART systems in sub-mammalian vertebrates and seek the answer why the system is shaped the way it is. We enquire into the conservation of the CART system and appreciate its functional diversity across the phyla.

View all citing articles on Scopus

View full text

Distribution of metabotropic glutamate receptor 7 messenger RNA in the developing and adult rat brain

Abstract

J. biol. Chem.

Brain Res.

Neuropharmacology

Brain Res.

Gen. Pharmac.

Neurosci. Lett.

Trends Neurosci.

Trends Neurosci.

Brain Res.

Brain Res.

Neuroscience

Brain Res.

Brain Res.

Trends Neurosci.

Prog. Neurobiol.

J. biol. Chem.

Neuron

Cell

Neuroscience

J. biol. Chem.

Eur. J. Pharmac.

Trends pharmac. Sci.