Disease Progression ; Humans ; Neoplasms ; diagnosis ; metabolism ; Receptors, Metabotropic Glutamate ; metabolism

The aim of the present study was to explore the role of group II and III metabotropic glutamate receptors (mGluRs) in carotid body plasticity induced by chronic intermittent hypoxia (CIH) in rats. Sprague Dawley (SD) rats were treated with CIH in Oxycycler A84 hypoxic chamber for 4 weeks, and the tail artery blood pressure was measured at the end of model preparation. RT-qPCR was performed to examine the mRNA expression levels of mGluR2/3/8 in rat carotid body. Carotid sinus nerve activity was detected by ex vivo carotid sinus nerve discharge recording technique, and acute intermittent hypoxia (AIH) was administered to induce carotid body sensory long-term facilitation (sLTF), in order to observe the role of group II and group III mGluRs in carotid body plasticity induced by CIH. The results showed that: 1) After 4 weeks of CIH exposure, the blood pressure of rats increased significantly; 2) CIH down-regulated the mRNA levels of mGluR2/3, and up-regulated the mRNA level of mGluR8 in the carotid body; 3) AIH induced sLTF in carotid body of CIH group. In the CIH group, activation of group II mGluRs had no effect on sLTF of carotid body, while activation of group III mGluRs completely inhibited sLTF. These results suggest that CIH increases blood pressure in rats, and group III mGluRs play an inhibitory role in CIH-induced carotid body plasticity in rats.
Rats ; Animals ; Carotid Body/metabolism* ; Rats, Sprague-Dawley ; Hypoxia ; Receptors, Metabotropic Glutamate/metabolism* ; RNA, Messenger/metabolism*

The purpose of the present study was to explore the role of carotid body metabotropic glutamate receptor 1 (mGluR1) in chronic intermittent hypoxia (CIH)-induced carotid body plasticity. Sprague Dawley (SD) rats were exposed to CIH (6%-21% O₂, 4 min/cycle, 8 h/day) for 4 weeks. The blood pressure of rats was monitored non-invasively by tail-cuff method under consciousness. RT-qPCR was used to examine the mRNA expression level of mGluR1 in rat carotid body. Western blot was used to detect the protein expression level of mGluR1 in rat carotid body. The role of mGluR1 in CIH-induced carotid body sensory long-term facilitation (sLTF) was investigated by ex vivo carotid sinus nerve discharge recording, and the carotid body sLTF was evoked by a 10-episode of repetitive acute intermittent hypoxia (AIH: 1 min of 5% O₂ interspersed with 5 min of 95% O₂). The results showed that: 1) CIH increased the systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.005) and mean arterial blood pressure (P < 0.001) of rats; 2) CIH decreased the mRNA and protein levels of mGluR1 in the rat carotid body (P < 0.01); 3) 4 weeks of CIH induced carotid body sLTF significantly, exhibiting as an increasing baseline sensory activity during post-AIH, which was inhibited by application of an agonist of group I metabotropic glutamate receptors, (S)-3,5-dihydroxyphenylglycine (DHPG), during sLTF induction (P < 0.005). In summary, these results suggest that activation of mGluR1 inhibits CIH-induced carotid body plasticity in rats.
Rats ; Animals ; Carotid Body/metabolism* ; Rats, Sprague-Dawley ; Hypoxia ; Receptors, Metabotropic Glutamate/metabolism* ; RNA, Messenger/metabolism*

OBJECTIVETo investigate the expression of metabotropic glutamate receptor 5 (mGluR5) and its cellular distribution in the frontal cortex, ventricular zone (VZ) and subventricular zone (SVZ) in human fetuses.

METHODSAccording to the gestational age, the collected fetuses were divided into 4 groups, namely 9-11 weeks, 14-16 weeks, 22-24 weeks and 32-36 weeks. Brain tissue blocks including the frontal lobe or VZ/SVZ were prepared into slices, and the expression pattern and cellular distribution of mGluR5 in the frontal cortex and VZ/SVZ were observed by immunohistochemistry or immunofluorescence.

RESULTSmGluR5 immunoreactivity was present in the cell membrane in the frontal cortex, VZ and SVZ from the 9th to 36th weeks and the immunoreactivity in the marginal zone (MZ) and cortical plate (CP) was markedly stronger than that in VZ and SVZ. The cells expressing mGluR5 included neural stem/progenitor cells in the VZ and SVZ, immature neurons in the VZ and MZ, and numerous mature neurons in the CP.

CONCLUSIONmGluR5 is expressed by a variety of cells such as neural stem cells in the frontal cortex, VZ and SVZ in human fetus, suggesting a role of mGluR5 in the development of human cerebral cortex.

Cerebral Cortex ; cytology ; Cerebral Ventricles ; cytology ; metabolism ; Fetus ; cytology ; metabolism ; Frontal Lobe ; cytology ; metabolism ; Humans ; Neural Stem Cells ; cytology ; metabolism ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism

OBJECTIVE: Studies revealed that cerebellar flocculus-paraflocculus complex plays an important in vestibular compensation. To observe the expression change of Group I mGluRs in flocculus following left unilateral labyrinthectomy (UL). METHOD: After setting left labyrinthectomy, the change of Group I mGluRs was detected by RT-PCR. RESULT: Group I mGluR5 was induced increase in both side flocculus after unilateral labyrinthectomy. By contrast, mGluR1 was induced decrease. However, that of the lesioned side was stronger than that of the unlesioned side. CONCLUSION UL can induce change of Group I mGluRs in the flocculus. The fall in the resting discharge of the primary vestibular afferents and/or in the deafferented central vestibular neurons may cause the change of mGluRs. But the significance of the change of mGluRs in the vestibular compensation is still unknown.
Animals ; Cerebellar Nuclei ; metabolism ; Male ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism ; Vestibular Nuclei ; metabolism ; Vestibule, Labyrinth ; metabolism

OBJECTIVE: To observe the expression of mGluR5 in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL). METHOD: Thirty Wistar rats were randomly divided into two groups. Twenty four animals received unilateral labyrinthectomy while the others maintained labyrinthine well. After setting left labyrinthine, the change of mGluR5 was induced by immunohistochemistry, in situ hybridization. RESULT: mGluR5 was increased in lesioned side MVN after unilateral labyrinthectomy. The 12 h post-UL was highest. Then it was decrease in 36 h post-UL, while 7 d post-UL was same as control group. The change of contralateral was same as that in ipsilateral. CONCLUSION UL can induce increase of mGluR5 in the MVN. The reduced resting discharge in the primary vestibular afferents or in the central vestibular neurons may be responsible for the change of mGluR5. However the significance of the change of mGluR1 in the vestibular compensation is still unknown.
Animals ; Male ; Postoperative Period ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism ; Vestibular Nuclei ; metabolism ; Vestibule, Labyrinth ; metabolism ; surgery

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is the most abundant kinase within excitatory synapses in the mammalian brain. It interacts with and phosphorylates a large number of synaptic proteins, including major ionotropic glutamate receptors (iGluRs) and group I metabotropic glutamate receptors (mGluRs), to constitutively and/or activity-dependently regulate trafficking, subsynaptic localization, and function of the receptors. Among iGluRs, the N-methyl-D-aspartate receptor (NMDAR) is a direct target of CaMKII. By directly binding to an intracellular C-terminal (CT) region of NMDAR GluN2B subunits, CaMKII phosphorylates a serine residue (S1303) in the GluN2B CT. CaMKII also phosphorylates a serine site (S831) in the CT of α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid receptors. This phosphorylation enhances channel conductance and is critical for synaptic plasticity. In addition to iGluRs, CaMKII binds to the proximal CT region of mGluR1a, which enables the kinase to phosphorylate threonine 871. Agonist stimulation of mGluR1a triggers a CaMKII-mediated negative feedback to facilitate endocytosis and desensitization of the receptor. CaMKII also binds to the mGluR5 CT. This binding seems to anchor and accumulate inactive CaMKII at synaptic sites. Active CaMKII dissociates from mGluR5 and may then bind to adjacent GluN2B to mediate the mGluR5-NMDAR coupling. Together, glutamate receptors serve as direct substrates of CaMKII. By phosphorylating these receptors, CaMKII plays a central role in controlling the number and activity of the modified receptors and determining the strength of excitatory synaptic transmission.
Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; metabolism ; Neuronal Plasticity ; Phosphorylation ; Receptor, Metabotropic Glutamate 5 ; metabolism ; Receptors, Metabotropic Glutamate ; metabolism ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Serine ; metabolism ; Synapses ; Synaptic Transmission

AIMTo investigate the protective effect of mGluR1 antisense oligonucleotides and mGluR5 antisense oligonucleotides on impairment of cultured mouse cerebral cortical neurons induced by sodium glutamate (Glu).

METHODSNeuron damage induced by Glu as well as the action of mGluR1 antisense oligonucleotides and mGluR5 antisense oligonucleotides were measured by determining the leakage of lactate dehydrogenase (LDH) from neurons. Immunocytochemistry method was used to detect the expression of anti-mGluRl a and anti-mGluR5. Morphological changes of primary cortical neurons were observed by phase contrast microscope.

RESULTSFollowing the exposure of the cells to 0.1 mmol x L(-1) Glu for 15 min, LDH leakage from neurons increased. mGluR1 antisense oligonucleotides and mGluR5 antisense oligonucleotides(6 or 8 micromol x L(-1)) as well as 50 micromol x L(-1) LY367385 reduced the LDH leakage. mGluR1alpha and mGluR5 immunopositive cells showed in cultured neurons.

CONCLUSIONThe protective effects of mGluR1 antisense oligonucleotides and mGluR5 antisense oligonucleotides on neurons damaged by Glu may relate to antagonizing mGluR1a or mGItlR5.

Animals ; Cells, Cultured ; Cerebral Cortex ; cytology ; Mice ; Mice, Inbred Strains ; Neurons ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Oligonucleotides, Antisense ; Receptors, Metabotropic Glutamate ; genetics ; Sodium Glutamate ; toxicity

OBJECTIVETo investigate the expression changes of metabotropic glutamate receptor 5 (mGluR5) in neuropathic pain.

METHODSEighty-four adult male Sprague Dawley rats weighing 180-220 g were randomly divided into 7 groups (n = 12) : control group; S3, S7, and S14 groups: rats received the sham operation, the mechanical pain threshold was measured, and then the rats were decapitated and the ipsilateral lumbar spinal cord dorsal horn and dorsal root ganglion (DRG) samples were obtained on the 3rd, 7th, 14th postoperative day, respectively; C3, C7, and C14 groups: the chronic sciatic nerve constriction (CCI) model was established, the mechanical pain threshold was measured and the samples were obtained on the 3rd, 7th, 14th postoperative day, respectively. The expression level of mGluR5 mRNA and protein in the spinal cord and DRG were measured using the reverse transcriptase polymerase chain reaction and Western blot.

RESULTSIn the CCI group, the mechanical pain threshold in each observation day was significantly lower than in the sham operation group (P < 0.05). In the spinal cord, the expressions of mGluR5 mRNA and protein were significantly elevated in the C3 group than in the S3 and the control group (P < 0.05). On the 7th and the 14th postoperative day, no significant difference was found in the expression of mGluR5 mRNA and protein between CCI groups and the sham operation groups or the control group. No change was detected in DRG mRNA or protein.

CONCLUSIONmGluR5 is differentially expressed in spinal cord in response to neuropathic pain, which suggests that mGluR5 may be involved in the mechanism of neuropathic pain.

Animals ; Disease Models, Animal ; Ganglia, Spinal ; metabolism ; Male ; Neuralgia ; metabolism ; Pain Threshold ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; genetics ; metabolism ; Sciatic Neuropathy ; metabolism ; Spinal Cord ; metabolism

AIMTo explore roles of metabotropic glutamate receptor1/5 (mGluR1/5) in the induction of brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP), influences of mGluR1/5 ligand (s)-4-carboxy-3-hydroxy- phenylglycine ((s)-4C3HPG) on the induction of BIT and expression of glial fibrillary acidic protein (GFAP) in the hippocampus were observed.

METHODSThionin staining and GFAP immunohistochemistry staining in rat 4 vessel occlusion (4VO) brain ischemic model was used. Thirty-six rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 4 groups: sham group; ischemic insult group, BIT group and (s)-4C3HPG group. According to dosages of (s)-4C3HPG used, the (s)-4C3HPG group, was further divided into 0.2 mg, 0.04 mg and 0.008 mg subgroups. All the rats were killed 7 d after the operation or the final ischemic treatment.

RESULTS(1) The ischemic insult for 8 min increased the histological grade (HG), decreased the pyramidal neuronal density (ND) and increased the expression of GFAP significantly (P < 0.05 vs sham) (2) The CIP prevented the above injury changes in the BIT group. (3) The protective effects of the CIP were blocked by (s)-4C3HFG, as manifested by significant increases in HG and decreases in ND in the (s)-4C3HPG group (P < 0.05 vs sham and BIT groups). The changes were proportional with the dosages of (s)-4C3HPG used.

CONCLUSION(s)-4C3HPG could block the induction of BIT induced by CIP, suggested that mGluR1/5 participate in the induction of BIT.

Animals ; Brain Ischemia ; metabolism ; physiopathology ; Electroencephalography ; Glial Fibrillary Acidic Protein ; metabolism ; Glycine ; analogs & derivatives ; pharmacology ; Ischemic Preconditioning ; Male ; Neuroglia ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; antagonists & inhibitors ; metabolism