{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:38:41Z","timestamp":1793140721985,"version":"4.5.0"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a common neurodegenerative disorder of middle-aged and elderly people, clinically characterized by resting tremor, myotonia, reduced movement, and impaired postural balance. Clinically, patients with PD are often administered levodopa (L-DOPA) to improve their symptoms. However, after years of L-DOPA treatment, most patients experience complications of varying severity, including the \u201con-off phenomenon\u201d, decreased efficacy, and levodopa-induced dyskinesia (LID). The development of LID can seriously affect the quality of life of patients, but its pathogenesis is unclear and effective treatments are lacking. Glutamic acid (Glu)-mediated changes in synaptic plasticity play a major role in LID. The N-methyl-D-aspartic acid receptor (NMDAR), an ionotropic glutamate receptor, is closely associated with synaptic plasticity, and neuroinflammation can modulate NMDAR activation or expression; in addition, neuroinflammation may be involved in the development of LID. However, it is not clear whether NMDA receptors are co-regulated with neuroinflammation during LID formation. Here we review how neuroinflammation mediates the development of LID through the regulation of NMDA receptors, and assess whether common anti-inflammatory drugs and NMDA receptor antagonists may be able to mitigate the development of LID through the regulation of central neuroinflammation, thereby providing a new theoretical basis for finding new therapeutic targets for LID.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1253273","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T05:47:09Z","timestamp":1696398429000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Levodopa-induced dyskinesia: interplay between the N-methyl-D-aspartic acid receptor and neuroinflammation"],"prefix":"10.3389","volume":"14","author":[{"given":"Fanshi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Tuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zucai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and treatment of Parkinson disease: A review","volume":"323","author":"Armstrong","year":"2020","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad064","article-title":"Impaired dopamine release in Parkinson\u2019s disease","volume":"146","author":"Cramb","year":"2023","journal-title":"Brain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1124\/pharmrev.122.000618","article-title":"Dopamine, immunity, and disease","volume":"75","author":"Channer","year":"2023","journal-title":"Pharmacol Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.0183","article-title":"Physical frailty, genetic predisposition, and incident Parkinson disease","volume":"80","author":"Zheng","year":"2023","journal-title":"JAMA Neurol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2018.10.014","article-title":"Parkinson\u2019s disease","volume":"103","author":"Reich","year":"2019","journal-title":"Med Clin North Am"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.625166","article-title":"Systemic inflammation increases the susceptibility to levodopa-induced dyskinesia in 6-OHDA lesioned rats by targeting the NR2B-medicated PKC\/MEK\/ERK pathway","volume":"12","author":"Yan","year":"2021","journal-title":"Front Aging Neurosci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2011.05.009","article-title":"Factors related to functional independence in females with Parkinson\u2019s disease: a systematic review","volume":"69","author":"Roland","year":"2011","journal-title":"Maturitas"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20132","article-title":"Natural history and syndromic associations of orthostatic tremor: a review of 41 patients","volume":"19","author":"Gerschlager","year":"2004","journal-title":"Mov Disord"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-018-1900-6","article-title":"Levodopa-induced dyskinesia: clinical features, incidence, and risk factors","volume":"125","author":"Tran","year":"2018","journal-title":"J Neural Transm (Vienna)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27900","article-title":"Neuroinflammation: fanning the fire of L-dopa-induced dyskinesia","volume":"34","author":"Bishop","year":"2019","journal-title":"Movement Disord"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27799","article-title":"Immunomodulatory drugs alleviate l-dopa-induced dyskinesia in a rat model of Parkinson\u2019s disease","volume":"34","author":"Boi","year":"2019","journal-title":"Mov Disord"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2019.05.019","article-title":"Late aging-associated increases in L-DOPA-induced dyskinesia are accompanied by heightened neuroinflammation in the hemi-parkinsonian rat","volume":"81","author":"Lanza","year":"2019","journal-title":"Neurobiol Aging"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.683577","article-title":"Resveratrol alleviates levodopa-induced dyskinesia in rats","volume":"12","author":"Zheng","year":"2021","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1111\/ejn.13482","article-title":"l-DOPA-induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role","volume":"45","author":"Carta","year":"2017","journal-title":"Eur J Neurosci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-021-00345-x","article-title":"Interferon-\u03b3 Involvement in the neuroinflammation associated with parkinson\u2019s disease and L-DOPA-induced dyskinesia","volume":"39","author":"Ferrari","year":"2021","journal-title":"Neurotox Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.625166","article-title":"Systemic inflammation increases the susceptibility to levodopa-induced dyskinesia in 6-OHDA lesioned rats by targeting the NR2B-medicated PKC\/MEK\/ERK pathway","volume":"12","author":"Yan","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2101-1","article-title":"Current disease modifying approaches to treat Parkinson\u2019s disease","volume":"73","author":"Lindholm","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.805388","article-title":"Molecular mechanisms and therapeutic strategies for levodopa-induced dyskinesia in Parkinson\u2019s disease: A perspective through preclinical and clinical evidence","volume":"13","author":"Bandopadhyay","year":"2022","journal-title":"Front Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s12974-022-02528-5","article-title":"Transient neuroinflammation following surgery contributes to long-lasting cognitive decline in elderly rats via dysfunction of synaptic NMDA receptor","volume":"19","author":"Chen","year":"2022","journal-title":"J Neuroinflamm"},{"key":"B20","doi-asserted-by":"publisher","first-page":"597","DOI":"10.3390\/biom12040597","article-title":"Cerebral glutamate regulation and receptor changes in perioperative neuroinflammation and cognitive dysfunction","volume":"12","author":"Zhang","year":"2022","journal-title":"Biomolecules"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02201-z","article-title":"Pivotal role of Fyn kinase in Parkinson\u2019s disease and levodopa-induced dyskinesia: a novel therapeutic target","volume":"58","author":"Angelopoulou","year":"2021","journal-title":"Mol Neurobiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.schres.2021.11.045","article-title":"N-Methyl-d-Aspartate receptor and inflammation in dorsolateral prefrontal cortex in schizophrenia","volume":"240","author":"Rahman","year":"2022","journal-title":"Schizophr Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.09.005","article-title":"The combination of the opioid glycopeptide MMP-2200 and a NMDA receptor antagonist reduced l-DOPA-induced dyskinesia and MMP-2200 by itself reduced dopamine receptor 2-like agonist-induced dyskinesia","volume":"141","author":"Flores","year":"2018","journal-title":"Neuropharmacology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00213-008-1135-6","article-title":"Effects of coincident 5-HT1A receptor stimulation and NMDA receptor antagonism on L-DOPA-induced dyskinesia and rotational behaviors in the hemi-parkinsonian rat","volume":"199","author":"Dupre","year":"2008","journal-title":"Psychopharmacol (Berl)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.10.021","article-title":"Synaptic plasticity may underlie l-DOPA induced dyskinesia","volume":"48","author":"Borgkvist","year":"2018","journal-title":"Curr Opin Neurobiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2016.00105","article-title":"Maladaptive synaptic plasticity in L-DOPA-induced dyskinesia","volume":"10","author":"Wang","year":"2016","journal-title":"Front Neural Circuits"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nn1040","article-title":"Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia","volume":"6","author":"Picconi","year":"2003","journal-title":"Nat Neurosci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn322","article-title":"Levodopa enhances synaptic plasticity in the substantia nigra pars reticulata of Parkinson\u2019s disease patients","volume":"132","author":"Prescott","year":"2009","journal-title":"Brain"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2018-318584","article-title":"The Movement disorder associated with NMDAR antibody-encephalitis is complex and characteristic: an expert video-rating study","volume":"90","author":"Varley","year":"2019","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B30","doi-asserted-by":"publisher","first-page":"102001","DOI":"10.1016\/j.arr.2023.102001","article-title":"Urgent needs of caregiving in ageing populations with Alzheimer\u2019s disease and other chronic conditions: Support our loved ones","volume":"90","author":"Culberson","year":"2023","journal-title":"Ageing Res Rev"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29508","article-title":"X-chromosome association study in latin american cohorts identifies new loci in Parkinson\u2019s disease","volume":"38","author":"Leal","year":"2023","journal-title":"Mov Disord"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011797","article-title":"Perivascular spaces in the basal ganglia and long-term motor prognosis in newly diagnosed Parkinson disease","volume":"96","author":"Chung","year":"2021","journal-title":"Neurology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"105650","DOI":"10.1016\/j.nbd.2022.105650","article-title":"Striatal synaptic dysfunction in dystonia and levodopa-induced dyskinesia","volume":"166","author":"Scarduzio","year":"2022","journal-title":"Neurobiol Dis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2003.07.003","article-title":"Levodopa-induced motor complications are associated with alterations of glutamate receptors in Parkinson\u2019s disease","volume":"14","author":"Calon","year":"2003","journal-title":"Neurobiol Dis"},{"key":"B35","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1124\/molpharm.120.000218","article-title":"The negative allosteric modulator EU1794-4 reduces single-channel conductance and Ca2+ Permeability of GluN1\/GluN2A N-methyl-D-aspartate receptors","volume":"99","author":"Perszyk","year":"2021","journal-title":"Mol Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/jpp\/rgab021","article-title":"Icariin ameliorates partial sciatic nerve ligation induced neuropathic pain in rats: an evidence of in silico and in vivo studies","volume":"73","author":"Pokkula","year":"2021","journal-title":"J Pharm Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.schres.2018.06.037","article-title":"Low plasma concentrations of N-methyl-D-aspartate receptor subunits as a possible biomarker for psychosis","volume":"202","author":"Loureiro","year":"2018","journal-title":"Schizophr Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-019-00036-7","article-title":"Subunit-specific effects of poricoic acid A on NMDA receptors","volume":"72","author":"Lee","year":"2020","journal-title":"Pharmacol Rep"},{"key":"B39","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3967\/bes2015.002","article-title":"Microwave exposure impairs synaptic plasticity in the rat hippocampus and PC12 cells through over-activation of the NMDA receptor signaling pathway","volume":"28","author":"Xiong","year":"2015","journal-title":"Biomed Environ Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00236","article-title":"Neuromodulatory effect of thymoquinone in attenuating glutamate-mediated neurotoxicity targeting the amyloidogenic and apoptotic pathway","volume":"9","author":"Fouad","year":"2018","journal-title":"Front Neurol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00426","article-title":"Endogenous glutamate excites myenteric calbindin neurons by activating group I metabotropic glutamate receptors in the mouse colon","volume":"13","author":"Swaminathan","year":"2019","journal-title":"Front Neurosci"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40035-021-00278-7","article-title":"Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration","volume":"11","author":"Verma","year":"2022","journal-title":"Transl Neurodegener"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1042\/BST0380493","article-title":"Synaptic dysfunction in Parkinson\u2019s disease","volume":"38","author":"Bagetta","year":"2010","journal-title":"Biochem Soc Trans"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-014-1176-4","article-title":"Therapeutic potential of targeting glutamate receptors in Parkinson\u2019s disease","volume":"121","author":"Finlay","year":"2014","journal-title":"J Neural Transm (Vienna)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00144","article-title":"Pharmacological treatments inhibiting levodopa-induced dyskinesias in MPTP-lesioned monkeys: brain glutamate biochemical correlates","volume":"5","author":"Morin","year":"2014","journal-title":"Front Neurol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00645-7","article-title":"The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1","volume":"40","author":"Krapivinsky","year":"2003","journal-title":"Neuron"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666151201185652","article-title":"mGlu5, dopamine D2 and adenosine A2A receptors in L-DOPA-induced dyskinesias","volume":"14","author":"Morin","year":"2016","journal-title":"Curr Neuropharmacol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/35016089","article-title":"Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity","volume":"405","author":"Lee","year":"2000","journal-title":"Nature"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2020.00230","article-title":"Rapamycin, by inhibiting mTORC1 signaling, prevents the loss of striatal bidirectional synaptic plasticity in a rat model of L-DOPA-induced dyskinesia","volume":"12","author":"Calabrese","year":"2020","journal-title":"Front Aging Neurosci"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.08.006","article-title":"Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models","volume":"71","author":"Thiele","year":"2014","journal-title":"Neurobiol Dis"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.04.002","article-title":"Derangement of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and extracellular signal-regulated kinase (ERK) dependent striatal plasticity in L-DOPA-induced dyskinesia","volume":"77","author":"Cerovic","year":"2015","journal-title":"Biol Psychiatry"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9177-9","article-title":"Changes in subcellular distribution and phosphorylation of GluR1 in lesioned striatum of 6-hydroxydopamine-lesioned and l-dopa-treated rats","volume":"31","author":"Ba","year":"2006","journal-title":"Neurochem Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07290.x","article-title":"Forelimb dyskinesia mediated by high-frequency stimulation of the subthalamic nucleus is linked to rapid activation of the NR2B subunit of N-methyl-D-aspartate receptors","volume":"32","author":"Quintana","year":"2010","journal-title":"Eur J Neurosci"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.06.009","article-title":"Effects of L-DOPA and STN-HFS dyskinesiogenic treatments on NR2B regulation in basal ganglia in the rat model of Parkinson\u2019s disease","volume":"48","author":"Quintana","year":"2012","journal-title":"Neurobiol Dis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.nbd.2019.03.012","article-title":"Hyperhomocysteinemia leads to exacerbation of ischemic brain damage: Role of GluN2A NMDA receptors","volume":"127","author":"Jindal","year":"2019","journal-title":"Neurobiol Dis"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.10.039","article-title":"M4 muscarinic receptor signaling ameliorates striatal plasticity deficits in models of L-DOPA-induced dyskinesia","volume":"88","author":"Shen","year":"2015","journal-title":"Neuron"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/j.neuron.2016.05.017","article-title":"M4 muscarinic receptor signaling ameliorates striatal plasticity deficits in models of L-DOPA-induced dyskinesia","volume":"90","author":"Shen","year":"2016","journal-title":"Neuron"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.09.021","article-title":"NMDA receptor GluN2D subunit participates to levodopa-induced dyskinesia pathophysiology","volume":"121","author":"Mellone","year":"2019","journal-title":"Neurobiol Dis"},{"key":"B59","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.physbeh.2019.01.005","article-title":"NMDA receptor in the hippocampus alters neurobehavioral phenotypes through inflammatory cytokines in rats with sporadic Alzheimer-like disease","volume":"202","author":"Amani","year":"2019","journal-title":"Physiol Behav"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59426","article-title":"PSD-95 expression controls L-DOPA dyskinesia through dopamine D1 receptor trafficking","volume":"122","author":"Porras","year":"2012","journal-title":"J Clin Invest"},{"key":"B61","doi-asserted-by":"publisher","first-page":"e200023","DOI":"10.1212\/NXI.0000000000200023","article-title":"Microglia as central protagonists in the chronic stress response","volume":"9","author":"Schramm","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: A field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"B63","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1186\/s13046-022-02535-7","article-title":"Microglia and metastases to the central nervous system: victim, ravager, or something else","volume":"41","author":"Caffarel","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00363-8","article-title":"Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration","volume":"3","author":"Xu","year":"2023","journal-title":"Nat Aging"},{"key":"B65","doi-asserted-by":"publisher","first-page":"100623","DOI":"10.1016\/j.bbih.2023.100623","article-title":"Effects of hydrogen gas inhalation on L-DOPA-induced dyskinesia","volume":"30","author":"Nascimento","year":"2023","journal-title":"Brain Behav Immun Health"},{"key":"B66","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.bbi.2020.07.044","article-title":"Levodopa partially rescues microglial numerical, morphological, and phagolysosomal alterations in a monkey model of Parkinson\u2019s disease","volume":"90","author":"Lecours","year":"2020","journal-title":"Brain Behav Immun"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2018.12.233","article-title":"Microglial-driven changes in synaptic plasticity: A possible role in major depressive disorder","volume":"102","author":"Innes","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.145581","article-title":"Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat","volume":"586","author":"Vikman","year":"2008","journal-title":"J Physiol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz105","article-title":"Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing","volume":"142","author":"Dedek","year":"2019","journal-title":"Brain"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3422-04.2004","article-title":"Group I metabotropic glutamate receptor NMDA receptor coupling and signaling cascade mediate spinal dorsal horn NMDA receptor 2B tyrosine phosphorylation associated with inflammatory hyperalgesia","volume":"24","author":"Guo","year":"2004","journal-title":"J Neurosci"},{"key":"B71","doi-asserted-by":"publisher","first-page":"15945","DOI":"10.1038\/srep15945","article-title":"Phosphorylation of NR2B NMDA subunits by protein kinase C in arcuate nucleus contributes to inflammatory pain in rats","volume":"5","author":"Bu","year":"2015","journal-title":"Sci Rep"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.07.025","article-title":"Regulating G protein activity by lipase-independent functions of phospholipase C","volume":"137","author":"Litosch","year":"2015","journal-title":"Life Sci"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-010-0140-x","article-title":"NMDA receptor, PKC and ERK prevent fos expression induced by the activation of group I metabotropic glutamate receptors in the spinal trigeminal subnucleus oralis","volume":"30","author":"Park","year":"2010","journal-title":"Mol Cells"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183702","article-title":"Longistyline C acts antidepressant in vivo and neuroprotection in vitro against glutamate-induced cytotoxicity by regulating NMDAR\/NR2B-ERK pathway in PC12 cells","volume":"12","author":"Liu","year":"2017","journal-title":"PloS One"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.02.051","article-title":"Ketamine-induced neurotoxicity blocked by N-Methyl-d-aspartate is mediated through activation of PKC\/ERK pathway in developing hippocampal neurons","volume":"673","author":"Jiang","year":"2018","journal-title":"Neurosci Lett"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2010.190","article-title":"Enhanced NMDA receptor NR1 phosphorylation and neuronal activity in the arcuate nucleus of hypothalamus following peripheral inflammation","volume":"32","author":"Peng","year":"2011","journal-title":"Acta Pharmacol Sin"},{"key":"B77","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl Neurodegener"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.678744","article-title":"Immune cells in the BBB disruption after acute ischemic stroke: targets for immune therapy","volume":"12","author":"Qiu","year":"2021","journal-title":"Front Immunol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1186\/s12974-019-1524-2","article-title":"An update on reactive astrocytes in chronic pain","volume":"16","author":"Li","year":"2019","journal-title":"J Neuroinflamm"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.00111","article-title":"ATP signaling controlling dyskinesia through P2X7 receptors","volume":"13","author":"Fonteles","year":"2020","journal-title":"Front Mol Neurosci"},{"key":"B81","doi-asserted-by":"publisher","first-page":"106133","DOI":"10.1016\/j.phrs.2022.106133","article-title":"CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson\u2019s disease","volume":"177","author":"Wang","year":"2022","journal-title":"Pharmacol Res"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.617085","article-title":"Contributive role of TNF-alpha to L-DOPA-induced dyskinesia in a unilateral 6-OHDA lesion model of Parkinson\u2019s disease","volume":"11","author":"Pereira","year":"2021","journal-title":"Front Pharmacol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"108895","DOI":"10.1016\/j.celrep.2021.108895","article-title":"TNF-\u03b1 and \u03b1-synuclein fibrils differently regulate human astrocyte immune reactivity and impair mitochondrial respiration","volume":"34","author":"Russ","year":"2021","journal-title":"Cell Rep"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.07.021","article-title":"Impeding the combination of astrocytic ASCT2 and NLRP3 by talniflumate alleviates neuroinflammation in experimental models of Parkinson\u2019s disease","volume":"13","author":"Liu","year":"2023","journal-title":"Acta Pharm Sin B"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-019-01133-0","article-title":"Significant roles of neuroinflammation in Parkinson\u2019s disease: therapeutic targets for PD prevention","volume":"42","author":"Lee","year":"2019","journal-title":"Arch Pharm Res"},{"key":"B86","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/s41392-023-01486-5","article-title":"Role of neuroinflammation in neurodegeneration development","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1871-20.2020","article-title":"\u03b1-synuclein oligomers induce glutamate release from astrocytes and excessive extrasynaptic NMDAR activity in neurons, thus contributing to synapse loss","volume":"41","author":"Trudler","year":"2021","journal-title":"J Neurosci"},{"key":"B88","doi-asserted-by":"publisher","first-page":"5992","DOI":"10.1523\/JNEUROSCI.2543-21.2022","article-title":"Selective ablation of Sod2 in astrocytes induces sex-specific effects on cognitive function, d-serine availability, and astrogliosis","volume":"42","author":"Baier","year":"2022","journal-title":"J Neurosci"},{"key":"B89","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/jnc.14041","article-title":"The noble gas xenon provides protection and trophic stimulation to midbrain dopamine neurons","volume":"142","author":"Lavaur","year":"2017","journal-title":"J Neurochem"},{"key":"B90","doi-asserted-by":"publisher","first-page":"110557","DOI":"10.1016\/j.celrep.2022.110557","article-title":"NMDA receptor-dependent prostaglandin-endoperoxide synthase 2 induction in neurons promotes glial proliferation during brain development and injury","volume":"38","author":"Zhou","year":"2022","journal-title":"Cell Rep"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2021.10.012","article-title":"Astrocytes render memory flexible by releasing D-serine and regulating NMDA receptor tone in the hippocampus","volume":"91","author":"Koh","year":"2022","journal-title":"Biol Psychiatry"},{"key":"B92","doi-asserted-by":"publisher","first-page":"3952","DOI":"10.1016\/j.cub.2022.07.038","article-title":"Gliotransmission of D-serine promotes thirst-directed behaviors in Drosophila","volume":"32","author":"Park","year":"2022","journal-title":"Curr Biol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0801-20.2020","article-title":"D-serine signaling and NMDAR-mediated synaptic plasticity are regulated by system A-type of glutamine\/D-serine dual transporters","volume":"40","author":"Bodner","year":"2020","journal-title":"J Neurosci"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00239","article-title":"Diversity of astroglial effects on aging- and experience-related cortical metaplasticity","volume":"11","author":"Lalo","year":"2018","journal-title":"Front Mol Neurosci"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2014.10.017","article-title":"Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson\u2019s disease","volume":"73","author":"Bortolanza","year":"2015","journal-title":"Neurobiol Dis"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr165","article-title":"Vascular endothelial growth factor is upregulated by L-dopa in the parkinsonian brain: implications for the development of dyskinesia","volume":"134","author":"Ohlin","year":"2011","journal-title":"Brain"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.718324","article-title":"Modulation of glial function in health, aging, and neurodegenerative disease","volume":"15","author":"Hanslik","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00278","article-title":"Neuromodulation of glial function during neurodegeneration","volume":"14","author":"Stevenson","year":"2020","journal-title":"Front Cell Neurosci"},{"key":"B99","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.neuroscience.2023.02.004","article-title":"ONO-2506 can delay levodopa-induced dyskinesia in the early stage","volume":"523","author":"Yuan","year":"2023","journal-title":"Neuroscience"},{"key":"B100","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.cell.2009.01.038","article-title":"A Nurr1\/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death","volume":"137","author":"Saijo","year":"2009","journal-title":"Cell"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03892-7","article-title":"A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis","volume":"597","author":"Absinta","year":"2021","journal-title":"Nature"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-019-09839-0","article-title":"Inhibition of bruton\u2019s tyrosine kinase modulates microglial phagocytosis: therapeutic implications for Alzheimer\u2019s disease","volume":"14","author":"Keaney","year":"2019","journal-title":"J Neuroimmune Pharmacol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413863200","article-title":"Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport","volume":"280","author":"Takeuchi","year":"2005","journal-title":"J Biol Chem"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600504200","article-title":"Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner","volume":"281","author":"Takeuchi","year":"2006","journal-title":"J Biol Chem"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90162-6","article-title":"Glutamate neurotoxicity and diseases of the nervous system","volume":"1","author":"Choi","year":"1988","journal-title":"Neuron"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0216fje","article-title":"Mice deficient in TNF receptors are protected against dopaminergic neurotoxicity: implications for Parkinson\u2019s disease","volume":"16","author":"Sriram","year":"2002","journal-title":"FASEB J"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5643-07.2008","article-title":"Mechanisms of microglia-mediated neurotoxicity in a new model of the stroke Penumbra","volume":"28","author":"Kaushal","year":"2008","journal-title":"J Neurosci"},{"key":"B108","doi-asserted-by":"publisher","first-page":"104982","DOI":"10.1016\/j.neuint.2021.104982","article-title":"The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases","volume":"144","author":"Trivi\u00f1o","year":"2021","journal-title":"Neurochem Int"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.08.062","article-title":"Modulation of CaMKIIa-GluN2B interaction in levodopa-induced dyskinesia in 6-OHDA-lesioned Parkinson\u2019s rats","volume":"107","author":"Wang","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1172\/JCI133398","article-title":"Striatal Kir2 K+ channel inhibition mediates the antidyskinetic effects of amantadine","volume":"130","author":"Shen","year":"2020","journal-title":"J Clin Invest"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-016-9720-7","article-title":"Vitamin D treatment attenuates neuroinflammation and dopaminergic neurodegeneration in an animal model of Parkinson\u2019s disease, shifting M1 to M2 microglia responses","volume":"12","author":"Calvello","year":"2017","journal-title":"J Neuroimmune Pharmacol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.06.011","article-title":"Neuroinflammation in the generation of post-transplantation dyskinesia in Parkinson\u2019s disease","volume":"32","author":"Lane","year":"2008","journal-title":"Neurobiol Dis"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2006.40","article-title":"Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson\u2019s disease","volume":"38","author":"Kim","year":"2006","journal-title":"Exp Mol Med"},{"key":"B114","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1186\/1742-2094-9-275","article-title":"L-glutamate released from activated microglia downregulates astrocytic L-glutamate transporter expression in neuroinflammation: the \u2018collusion\u2019 hypothesis for increased extracellular L-glutamate concentration in neuroinflammation","volume":"9","author":"Takaki","year":"2012","journal-title":"J Neuroinflamm"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22481","article-title":"Expression, subunit composition, and function of AMPA-type glutamate receptors are changed in activated microglia; possible contribution of GluA2 (GluR-B)-deficiency under pathological conditions","volume":"61","author":"Beppu","year":"2013","journal-title":"Glia"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24046","article-title":"Astrocyte-selective STAT3 knockdown rescues methamphetamine withdrawal-disrupted spatial memory in mice via restoring the astrocytic capacity of glutamate clearance in dCA1","volume":"69","author":"Shi","year":"2021","journal-title":"Glia"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22368","article-title":"Self-induced accumulation of glutamate in striatal astrocytes and basal ganglia excitotoxicity","volume":"60","author":"Morales","year":"2012","journal-title":"Glia"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S80174","article-title":"Ranitidine reduced levodopa-induced dyskinesia by remodeling neurochemical changes in hemiparkinsonian model of rats","volume":"11","author":"Shi","year":"2015","journal-title":"Neuropsychiatr Dis Treat"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.05.010","article-title":"Inhibition of striatal cholinergic interneuron activity by the Kv7 opener retigabine and the nonsteroidal anti-inflammatory drug diclofenac","volume":"137","author":"Paz","year":"2018","journal-title":"Neuropharmacology"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2022.2153036","article-title":"Dyskinesia and Parkinson\u2019s disease: animal model, drug targets, and agents in preclinical testing","volume":"26","author":"Cesaroni","year":"2022","journal-title":"Expert Opin Ther Targets"},{"key":"B121","doi-asserted-by":"publisher","first-page":"104646","DOI":"10.1016\/j.nbd.2019.104646","article-title":"Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia","volume":"134","author":"Rentsch","year":"2020","journal-title":"Neurobiol Dis"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00017-Z","article-title":"Different binding affinities of NMDA receptor channel blockers in various brain regions\u2013indication of NMDA receptor heterogeneity","volume":"34","author":"Bresink","year":"1995","journal-title":"Neuropharmacology"},{"key":"B123","doi-asserted-by":"publisher","first-page":"113413","DOI":"10.1016\/j.expneurol.2020.113413","article-title":"Preclinical evidence in support of repurposing sub-anesthetic ketamine as a treatment for L-DOPA-induced dyskinesia","volume":"333","author":"Bartlett","year":"2020","journal-title":"Exp Neurol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00017-Z","article-title":"Different binding affinities of NMDA receptor channel blockers in various brain regions\u2014Indication of NMDA receptor heterogeneity","volume":"34","author":"Bresink","year":"1995","journal-title":"Neuropharmacology"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1159\/000444278","article-title":"Case reports showing a long-term effect of subanesthetic ketamine infusion in reducing L-DOPA-induced dyskinesias","volume":"8","author":"Sherman","year":"2016","journal-title":"Case Rep Neurol"},{"key":"B126","doi-asserted-by":"publisher","first-page":"136251","DOI":"10.1016\/j.neulet.2021.136251","article-title":"Evaluation of microglia in a rodent model of Parkinson\u2019s disease primed with L-DOPA after sub-anesthetic ketamine treatment","volume":"765","author":"Pottenger","year":"2021","journal-title":"Neurosci Lett"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-019-02015-x","article-title":"Assessment of plasma creatine kinase as biomarker for levodopa-induced dyskinesia in Parkinson\u2019s disease","volume":"126","author":"Delamarre","year":"2019","journal-title":"J Neural Transm (Vienna)"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020945","article-title":"Simvastatin prevents dopaminergic neurodegeneration in experimental parkinsonian models: the association with anti-inflammatory responses","volume":"6","author":"Yan","year":"2011","journal-title":"PloS One"},{"key":"B129","doi-asserted-by":"publisher","first-page":"121049","DOI":"10.1016\/j.lfs.2022.121049","article-title":"Agmatine-mediated inhibition of NMDA receptor expression and amelioration of dyskinesia via activation of Nrf2 and suppression of HMGB1\/RAGE\/TLR4\/MYD88\/NF-\u03baB signaling cascade in rotenone lesioned rats","volume":"311","author":"Azar","year":"2022","journal-title":"Life Sci"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000004065","article-title":"Agmatine protects against the progression of sepsis through the imidazoline I2 receptor-ribosomal S6 kinase 2-nuclear factor-\u03baB signaling pathway","volume":"48","author":"Li","year":"2020","journal-title":"Crit Care Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1253273\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T05:47:15Z","timestamp":1696398435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1253273\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,4]]},"references-count":130,"alternative-id":["10.3389\/fimmu.2023.1253273"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1253273","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,4]]},"article-number":"1253273"}}