ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Mechanisms of dopamine D1 receptor-mediated ERK1/2 activation in the parkinsonian striatum and their modulation by metabotropic glutamate receptor type 5.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Lactate dynamics in Parkinson's disease: striatal circuit vulnerability, biomarker potential, and therapeutic windows.Molecular medicine (Cambridge, Mass.) · 2026Review
- Rapid and sustained antidepressant effects of tubastatin A in a mouse model of depression.Scientific reports · 2025Article
- Role of P11 through serotonergic and glutamatergic pathways in LID.Molecular biology reports · 2023Review
- Effects of DPTQ, a novel positive allosteric modulator of the dopamine D1 receptor, on spontaneous eye blink rate and spatial working memory in the nonhuman primate.Psychopharmacology · 2023Article
- Purkinje cell dopaminergic inputs to astrocytes regulate cerebellar-dependent behavior.Nature communications · 2023Article
- Preserved Motility after Neonatal Dopaminergic Lesion Relates to Hyperexcitability of Direct Pathway Medium Spiny Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum.International journal of molecular sciences · 2022Article
- Group I mGluRs in Therapy and Diagnosis of Parkinson's Disease: Focus on mGluR5 Subtype.Biomedicines · 2022Review
- Segregation of D1 and D2 dopamine receptors in the striatal direct and indirect pathways: An historical perspective.Frontiers in synaptic neuroscience · 2022Review
- Molecular Mechanisms and Therapeutic Strategies for Levodopa-Induced Dyskinesia in Parkinson's Disease: A Perspective Through Preclinical and Clinical Evidence.Frontiers in pharmacology · 2022Review
- Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.Journal of clinical medicine · 2021Review
- Loss of mGluR5 in D1 Receptor-Expressing Neurons Improves Stress Coping.International journal of molecular sciences · 2021Article
- Dyskinesia is Closely Associated with Synchronization of Theta Oscillatory Activity Between the Substantia Nigra Pars Reticulata and Motor Cortex in the Off L-dopa State in Rats.Neuroscience bulletin · 2021Article
- D1-mGlu5 heteromers mediate noncanonical dopamine signaling in Parkinson's disease.The Journal of clinical investigation · 2020Article
- mGluR5 Allosteric Modulation Promotes Neurorecovery in a 6-OHDA-Toxicant Model of Parkinson's Disease.Molecular neurobiology · 2020Article
- Genetic Knockdown of mGluR5 in Striatal D1R-Containing Neurons Attenuates L-DOPA-Induced Dyskinesia in Aphakia Mice.Molecular neurobiology · 2019Article
- Genetic enhancement of Ras-ERK pathway does not aggravate L-DOPA-induced dyskinesia in mice but prevents the decrease induced by lovastatin.Scientific reports · 2018Article
- Role of Mitogen Activated Protein Kinase Signaling in Parkinson's Disease.International journal of molecular sciences · 2018Review
- Effects of histone acetyltransferase inhibitors on L-DOPA-induced dyskinesia in a murine model of Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In animal models of Parkinson's disease, striatal overactivation of ERK1/2 via dopamine (DA) D1 receptors is the hallmark of a supersensitive molecular response associated with dyskinetic behaviors. Here we investigate the pathways involved in D1 receptor-dependent ERK1/2 activation using acute striatal slices from rodents with unilateral 6-hydroxydopamine (6-OHDA) lesions. Application of the dopamine D1-like receptor agonist SKF38393 induced ERK1/2 phosphorylation and downstream signaling in the DA-denervated but not the intact striatum. This response was mediated through a canonical D1R/PKA/MEK1/2 pathway and independent of ionotropic glutamate receptors but blocked by antagonists of L-type calcium channels. Coapplication of an antagonist of metabotropic glutamate receptor type 5 (mGluR5) or its downstream signaling molecules (PLC, PKC, IP3 receptors) markedly attenuated SKF38393-induced ERK1/2 activation. The role of striatal mGluR5 in D1-dependent ERK1/2 activation was confirmed in vivo in 6-OHDA-lesioned animals treated systemically with SKF38393. In one experiment, local infusion of the mGluR5 antagonist MTEP in the DA-denervated rat striatum attenuated the activation of ERK1/2 signaling by SKF38393. In another experiment, 6-OHDA lesions were applied to transgenic mice with a cell-specific knockdown of mGluR5 in D1 receptor-expressing neurons. These mice showed a blunted striatal ERK1/2 activation in response to SFK38393 treatment. Our results reveal that D1-dependent ERK1/2 activation in the DA-denervated striatum depends on a complex interaction between PKA- and Ca(2+)-dependent signaling pathways that is critically modulated by striatal mGluR5.
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