Disease relevance of Grm8

• The results show that pilocarpine-induced status epilepticus can lead to a downregulation of mGluR8 and suggest that the condition of SRS is associated with a deteriorated autoregulation of glutamate release [1].
• The present novel finding of induced expression of mGluR8 in astrocytes APISE suggests that it may be linked to gliosis [2].
• In this study we analyzed the function of presynaptic mGluR8 on terminals of the lateral perforant pathway in the pilocarpine model of limbic epilepsy [1].

High impact information on Grm8

• To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1-mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral [3].
• The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area [3].
• RT-PCR and immunological analyses indicated that mGluR4, a class III mGluR, was expressed and localized with alpha- and F cells, whereas no evidence for expression of other mGluRs, including mGluR8, was obtained [4].
• The metabotropic glutamate receptor (mGluR) cDNAs were originally cloned from rat, except for the mouse cDNA clone encoding mGluR8 [5].
• The pharmacological profile of mGluR8 is distinct among mGluRs but closely matches that of presynaptic inhibition in some central nervous system pathways [5].

Biological context of Grm8

• In both cases, the alternative splicing is generated by a similar out-of-frame insertion in the carboxyl-terminus that results in the replacement of the last 16 amino acids of mGluR7 and mGluR8 by 23 and 16 different amino acids, respectively [6].
• The present study is the first to provide a detailed mapping of mGluR8 within the autonomic nuclei of the medulla and suggests that this subtype may be involved in shaping synaptic transmission in these central nuclei [7].
• Down-regulation of mGluR8 in pilocarpine epileptic rats [1].

Anatomical context of Grm8

• In situ hybridization revealed prominent mGluR8 mRNA expression in olfactory bulb, pontine gray, lateral reticular nucleus of the thalamus, and piriform cortex [5].
• However, the agonist potencies were significantly higher for mGluR8a, b compared with mGluR7a,b. In Xenopus oocytes, glutamate evoked currents only with mGluR8 when coexpressed with Kir 3.1 and 3 [6].
• The intensity of mGluR8 staining was highest in the commissural and interstitial subnuclei at the level of the area postrema [7].
• Group III mGluRs such as mGluR8, because of their high affinity for glutamate, are particularly well suited to detect small changes in the concentration of this excitatory amino acid in the extracellular space [8].
• In vivo recording and labeling of an mGluR8-decorated and strongly M2-positive interneuron revealed a trilaminar cell with complex spike bursts during theta oscillations and strong discharge during sharp wave/ripple events [9].

Associations of Grm8 with chemical compounds

• We have demonstrated that alternatively spliced variants of mGluR8, mGluR8a and mGluR8b, have an overlapping distribution in the hippocampus, and besides perforant path terminals, they are expressed in the presynaptic active zone of boutons making synapses selectively with several types of GABAergic interneurons, primarily in the stratum oriens [9].
• The mGlur antagonists MTPG, MPPG and MAP4 should be useful in determining the roles of group II and III mGluRs in the central nervous system [10].

Regulatory relationships of Grm8

• Some mGluR8-positive boutons also expressed mGluR7 or vasoactive intestinal polypeptide [9].

Other interactions of Grm8

• Distribution analysis for mGluR7 and mGluR8 isoforms revealed that the two splice variants are generally coexpressed in the same brain areas [6].
• Rare neurons coexpressing calretinin and M2 were consistently targeted by mGluR8-positive boutons [9].
• The majority of M2-positive neurons were mGluR8 innervated, but a minority, which expresses somatostatin, was not [9].
• The superficial layer of the olfactory tubercle and layer Ia of the piriform cortex, the target areas of MOB, showed marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-like immunoreactivities (-LI), and rather weak mGluR2/3-LI [11].

Analytical, diagnostic and therapeutic context of Grm8

• By electron microscopy and double labelling study, the mGluR8 immunoreactive cells were identified as astrocytes [2].
• The expression of metabotropic glutamate receptor 8 (mGluR8) was studied in the rat hippocampus after pilocarpine-induced status epilepticus (APISE) by light immunohistochemistry and immunoelectron microscopy [2].

References