ArticleJournal of neuroscience research2005
N-methyl-D-aspartate and TrkB receptors protect neurons against glutamate excitotoxicity through an extracellular signal-regulated kinase pathway.
Article in Journal of neuroscience research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 71 citations in OpenAlex.
- Brain atrophy in autoimmune encephalitis: epidemiology, pathophysiology, clinical manifestations, treatment, and prognosis-an update.Journal of neurology · 2025Review
- Enhancing nerve regeneration in infraorbital nerve injury rat model: effects of vitamin B complex and photobiomodulation.Lasers in medical science · 2024Article
- Disease progression and brain atrophy in NMDAR encephalitis: Associated factor & clinical implication.Annals of clinical and translational neurology · 2022Article
- Symptomatologic pathomechanism ofEncephalitis (Seoul, Korea) · 2021Review
- Butanol Extract of Tinospora cordifolia Ameliorates Cognitive Deficits Associated with Glutamate-Induced Excitotoxicity: A Mechanistic Study Using Hippocampal Neurons.Neuromolecular medicine · 2020Article
- Exogenous brain-derived neurotrophic factor attenuates neuronal apoptosis and neurological deficits after subarachnoid hemorrhage in rats.Experimental and therapeutic medicine · 2019Article
- Medial prefrontal cortex exacerbates gastric dysfunction of rats upon restraint water‑immersion stress.Molecular medicine reports · 2019Article
- Glutamate release machinery is altered in the frontal cortex of rats with experimental autoimmune encephalomyelitis.Molecular neurobiology · 2015Article
- Enhanced vascular PI3K/Akt-NOX signaling underlies the peripheral NMDAR-mediated pressor response in conscious rats.Journal of cardiovascular pharmacology · 2014Article
- Preconditioning provides neuroprotection in models of CNS disease: paradigms and clinical significance.Progress in neurobiology · 2014Review
- Activation of M1 mAChRs by lesatropane rescues glutamate neurotoxicity in PC12 cells via PKC-mediated phosphorylation of ERK1/2.Bosnian journal of basic medical sciences · 2013Article
- Olesoxime protects embryonic cortical neurons from camptothecin intoxication by a mechanism distinct from BDNF.British journal of pharmacology · 2013Article
- Impairment of TrkB-PSD-95 signaling in Angelman syndrome.PLoS biology · 2013Article
- Molecular alterations associated with the NMDA preconditioning-induced neuroprotective mechanism against glutamate cytotoxicity.Journal of molecular neuroscience : MN · 2012Article
- Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer's disease.Neural regeneration research · 2012Article
- Neuroprotection by NMDA preconditioning against glutamate cytotoxicity is mediated through activation of ERK 1/2, inactivation of JNK, and by prevention of glutamate-induced CREB inactivation.Journal of molecular neuroscience : MN · 2012Article
- Amelioration of central cardiovascular regulatory dysfunction by tropomyocin receptor kinase B in a mevinphos intoxication model of brain stem death.British journal of pharmacology · 2011Article
- Addition of glutamate to serum-free culture promotes recovery of electrical activity in adult hippocampal neurons in vitro.Journal of neuroscience methods · 2010Article
- Transient focal ischemia results in persistent and widespread neuroinflammation and loss of glutamate NMDA receptors.NeuroImage · 2010Article
- Bone morphogenetic protein-6 promotes cerebellar granule neurons survival by activation of the MEK/ERK/CREB pathway.Molecular biology of the cell · 2009Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
N-Methyl-D-aspartate (NMDA) at a subtoxic concentration (100 microM) promotes neuronal survival against glutamate-mediated excitotoxicity via a brain-derived neurotrophic factor (BDNF) autocrine loop in cultured cerebellar granule cells. The signal transduction mechanism(s) underlying NMDA neuroprotection, however, remains elusive. The mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways alter gene expression and are involved in synaptic plasticity and neuronal survival. This study tested whether neuroprotective activation of NMDA receptors, together with TrkB receptors, coactivated the MAPK or PI3-K pathways to protect rat cerebellar neurons. NMDA receptor activation caused a concentration- and time-dependent activation of MAPK lasting 24 hr. This activation was blocked by the NMDA receptor antagonist MK-801 but was attenuated only partially by the tyrosine kinase inhibitor k252a, suggesting that activation of both NMDA and TrkB receptors are required for maximal neuroprotection. The MAPK kinase (MEK) inhibitor U0126 (10 microM) partially blocked NMDA neuroprotection, whereas LY294002, a selective inhibitor of the PI3-K pathway, did not affect the neuroprotective activity of NMDA. Glutamate excitotoxicity decreased bcl-2, bcl-X(L), and bax mRNA levels,. NMDA increases Bcl-2 and Bcl-X(L) protein levels and decreases Bax protein levels. NMDA and TrkB receptor activation thus converge on the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway to protect neurons against glutamate-mediated excitotoxicity. By increasing antiapoptotic proteins of the Bcl-2 family, NMDA receptor activation may also promote neuronal survival by preventing apoptosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.