scholarly journals Antidyskinetic Treatment with MTEP Affects Multiple Molecular Pathways in the Parkinsonian Striatum

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Jing-ya Lin ◽  
Zhen-guo Liu ◽  
Cheng-long Xie ◽  
Lu Song ◽  
Ai-juan Yan
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Treated Group ◽  
Indirect Pathway ◽  
Metabotropic Glutamate ◽  
Pkc Epsilon ◽  
Mglur5 Antagonist ◽  
Proenkephalin Mrna ◽  
Underlying Mechanisms ◽  
Dopaminergic Neuron Loss ◽  
Prodynorphin Mrna

Parkinson’s disease is characterized by dopaminergic neuron loss and dopamine (DA) depletion in the striatum. Standard treatment is still focused on the restoration of dopamine with exogenous L-Dopa, which however causes L-Dopa-induced dyskinesia (LID). Several studies have shown that antagonism of the metabotropic glutamate receptor 5 alleviates LID, but the underlying mechanisms have remained unclear. We set out to determine where this alleviation may depend on restoring the equilibrium between the two main striatofugal pathways. For this purpose, we examined molecular markers of direct and indirect pathway involvement (prodynorphin and proenkephalin, resp.) in a rat model of LID treated with the mGluR5 antagonist MTEP. Our results show that MTEP cotreatment significantly attenuates the upregulation of prodynorphin mRNA induced by L-Dopa while also decreasing the expression levels of proenkephalin mRNA. We also examined markers of the mGluR5-related PKC/MEK/ERK1/2 signaling pathway, finding that both the expression of PKC epsilon and the phosphorylation of MEK and ERK1/2 had decreased significantly in the MTEP-treated group. Taken together, our results show that pharmacological antagonism of mGluR5 normalizes several abnormal molecular responses in the striatum in this experimental model of LID.

scholarly journals Amygdala Metabotropic Glutamate Receptor 1 Influences Synaptic Transmission To Participate In Fentanyl-Induced Hyperalgesia In Rats

2022 ◽  
Author(s):  
Tianyu Bai ◽  
Hengling Chen ◽  
Wenwu Hu ◽  
Jingtao Liu ◽  
Xianguang Lin ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Central Nucleus ◽  
Metabotropic Glutamate ◽  
Metabotropic Glutamate Receptor 1 ◽  
Opioid Induced Hyperalgesia ◽  
Underlying Mechanisms ◽  
The Right ◽  
Fentanyl Group

Abstract The underlying mechanisms of opioid-induced hyperalgesia (OIH) remain unclear. Herein, we found that the protein expression of metabotropic glutamate receptor 1 (mGluR1) was significantly increased in the right, but not in the left laterocapsular division of central nucleus of the amygdala (CeLC) in OIH rats. In CeLC neurons, the frequency and the amplitude of mini-excitatory postsynaptic currents (mEPSCs) were significantly increased in fentanyl group which were decreased by acute application of a mGluR1 antagonist, A841720. Finally, the behavioral hypersensitivity could be reversed by A841720 microinjection into the right CeLC. These results show that the right CeLC mGluR1 is an important factor associated with OIH that enhances synaptic transmission and could be a potential drug target to alleviate fentanyl-induced hyperalgesia.

System Identification of mGluR-Dependent Long-Term Depression

2013 ◽  
Vol 25 (3) ◽  
pp. 650-670 ◽  
Author(s):  
Tim Tambuyzer ◽  
Tariq Ahmed ◽  
C. James Taylor ◽  
Daniel Berckmans ◽  
Detlef Balschun ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
System Identification ◽  
Metabotropic Glutamate Receptor ◽  
Synaptic Function ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Powerful Approach ◽  
Underlying Mechanisms ◽  
First Time

Recent advances have started to uncover the underlying mechanisms of metabotropic glutamate receptor (mGluR)–dependent long-term depression (LTD). However, it is not completely clear how these mechanisms are linked, and it is believed that several crucial mechanisms remain to be revealed. In this study, we investigated whether system identification (SI) methods can be used to gain insight into the mechanisms of synaptic plasticity. SI methods have been shown to be an objective and powerful approach for describing how sensory neurons encode information about stimuli. However, to our knowledge, it is the first time that SI methods have been applied to electrophysiological brain slice recordings of synaptic plasticity responses. The results indicate that the SI approach is a valuable tool for reverse-engineering of mGluR-LTD responses. We suggest that such SI methods can aid in unraveling the complexities of synaptic function.

scholarly journals L-DOPA-Induced Motor Impairment and Overexpression of Corticostriatal Synaptic Components Are Improved by the mGluR5 Antagonist MPEP in 6-OHDA-Lesioned Rats

ASN NEURO ◽  
2018 ◽  
Vol 10 ◽  
pp. 175909141881102 ◽  
Author(s):  
Yixian Huang ◽  
Haiyang Shu ◽  
Li Li ◽  
Tili Zhen ◽  
Junyan Zhao ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Metabotropic Glutamate Receptor ◽  
Motor Impairment ◽  
Term Therapy ◽  
Metabotropic Glutamate ◽  
Mglur5 Antagonist ◽  
Specific Antagonist ◽  
Targeted Inhibition ◽  
Long Term Therapy

Levodopa (L-DOPA) is still the most effective drug for the treatment of Parkinson’s disease (PD). However, the long-term therapy often triggers L-DOPA-induced dyskinesia (LID). Metabotropic glutamate receptor type 5 (mGluR5) is abundant in the basal ganglia, and its inhibition is thought to modulate postsynaptic excitatory synaptic transmission and glutamate hyperactivity in PD and LID. In this report, we examined the effects of mGluR5-specific antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) on LID and synaptic components in the PD model rat. We found the selective mGluR5 antagonist MPEP attenuated abnormal involuntary movements, prolonged the duration of rotational response, reversed the decrease of left forepaw adjusting steps, and reduced overexpression of striatal mGluR5 in the LID rats. Moreover, our results showed much thicker postsynaptic densities, narrower synapse cleft, as well as the increased ratio of perforated synapses induced by L-DOPA treatment, while coadministration of L-DOPA and MPEP reversed these postsynaptic effects. Finally, MPEP reduced overexpression of the two postsynaptic proteins (PSD-95 and SAP102) induced by L-DOPA treatment. Hence, these results provide evidence that aberrant neural plasticity at corticostriatal synapses in the striatum is closely correlated with the occurrence of LID, and targeted inhibition of mGluR5 by MPEP alleviates LID in the PD rat model.

scholarly journals Metabotropic Receptors 4 and the Immune Responses

2021 ◽  
Author(s):  
Zhuoya Wan ◽  
Song Li
Keyword(s):  
Central Nervous System ◽  
Immune Response ◽  
Immune Cells ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Receptors ◽  
Peripheral Tissues ◽  
Immune Modulators ◽  
Metabotropic Glutamate ◽  
Underlying Mechanisms ◽  
High Level

Neurotransmitters (NTs) have recently received increasing appreciation as important immune modulators. The immune cells express receptors for many classes of NTs and the communication between NTs and their receptors establish neuro-immune interactions for regulating effective immune response in both central nervous system (CNS) and peripheral tissues. Metabotropic Glutamate Receptor 4 (mGluR4) is expressed at high level in CNS and plays a role in various physiological and pathophysiological processes in CNS. Recently, mGluR4 has been reported to be expressed on immune cells and have an impact on regulating the immune system. This chapter summarized the works associated with the immunogenic function of mGluR4 and its potential underlying mechanisms.

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