Effect of NMDA, a Specific Agonist to NMDA Receptor Complex, on Rat Hippocampus

Motin, V. G.; Yasnetsov, V. V.

doi:10.1007/s10517-015-3053-z

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…The underlying mechanisms may be associated with the activation of NMDAR. NMDA activate NMDAR on hippocampal neurons, change synaptic plasticity and release excitatory neurotransmitters that condition and inhibit MK-801 in a non-competitive role to improve cell vitality ( 28 , 29 ). A further study has revealed that MK-801 treatment [0.2 mg/kg, intraperitoneal (IP)] increases NSC proliferation in the hippocampus of a rat model with Parkinson's disease ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells treated with MK‑801

et al. 2018

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The purpose of the present study was to investigate effects of N-methyl-D-aspartate (NMDA) on proliferation and apoptosis of hippocampal neural stem cells (NSCs) treated with dizocilpine (MK-801). Cultures of hippocampal NSCs were randomly divided into four groups consisting of an untreated control, cells treated with MK-801, NMDA and a combination of MK801 and NMDA (M+N). Proliferative and apoptotic responses for each of the experimental groups were determined by MTS and flow cytometry. The results revealed that MK-801 and NMDA exerted significant effects on hippocampal NSCs proliferation. Cell survival rates decreased in MK-801, NMDA and M+N treated groups compared with the control group. Cells survival rates in NMDA and M+N treated groups increased compared with the MK-801 treated group. MK-801 and NMDA were demonstrated to significantly affect apoptosis in hippocampal NSCs. Total and early stages of apoptosis in MK-801 and NMDA groups significantly increased compared with the control group. Total and early apoptosis of NSCs in the M+N group significantly decreased compared with MK-801 and NMDA groups. Late apoptosis of NSCs in MK-801 and NMDA groups significantly decreased compared with the control group. Late apoptosis of NSCs in the M+N group significantly increased compared with MK-801 and NMDA groups. The present study revealed that MK-801 inhibited proliferation and increased apoptosis in hippocampal NSCs. NMDA may reduce the neurotoxicity induced by MK-801, which may be associated with its activity towards NMDA receptors and may describe a novel therapeutic target for the treatment of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells treated with MK‑801

et al. 2018

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“…NMDARs are glutamate ionotropic receptors that play an important role in synaptic transmission and plasticity. Some NMDAR antagonists were identified to rapidly induce antidepressant effect by instant upregulation of expression of BDNF and spine formation [ 14 , 15 ]. Therefore, enhancement of neural plasticity can result from activation of PKA-CREB or inhibition of NMDA signaling.…”

Section: Introductionmentioning

confidence: 99%

Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

et al. 2017

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Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

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“…The NMDARs stimulation induces the influx of Ca 2+ through NMDARs and activates CaMKII, which then activates the RhoA-Rho-kinase pathway [7,11]. The NMDA (an NMDAR agonist) and high K + induced the CamKII autophosphorylation at Thr286 downstream of NMDARs [19,20]. To evaluate whether Rho-kinase phosphorylates PSD-93 downstream of NMDARs, striatal slices were treated with high K + or NMDA to induce Ca 2+ influx through NMDARs.…”

Section: Rho-kinase Phosphorylates Psd-93 At Thr612 In Striatal Slicesmentioning

confidence: 99%

Rho-Kinase/ROCK Phosphorylates PSD-93 Downstream of NMDARs to Orchestrate Synaptic Plasticity

Hossen

Funahashi

Faruk

et al. 2022

IJMS

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The N-methyl-D-aspartate receptor (NMDAR)-mediated structural plasticity of dendritic spines plays an important role in synaptic transmission in the brain during learning and memory formation. The Rho family of small GTPase RhoA and its downstream effector Rho-kinase/ROCK are considered as one of the major regulators of synaptic plasticity and dendritic spine formation, including long-term potentiation (LTP). However, the mechanism by which Rho-kinase regulates synaptic plasticity is not yet fully understood. Here, we found that Rho-kinase directly phosphorylated discs large MAGUK scaffold protein 2 (DLG2/PSD-93), a major postsynaptic scaffold protein that connects postsynaptic proteins with NMDARs; an ionotropic glutamate receptor, which plays a critical role in synaptic plasticity. Stimulation of striatal slices with an NMDAR agonist induced Rho-kinase-mediated phosphorylation of PSD-93 at Thr612. We also identified PSD-93-interacting proteins, including DLG4 (PSD-95), NMDARs, synaptic Ras GTPase-activating protein 1 (SynGAP1), ADAM metallopeptidase domain 22 (ADAM22), and leucine-rich glioma-inactivated 1 (LGI1), by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among them, Rho-kinase increased the binding of PSD-93 to PSD-95 and NMDARs. Furthermore, we found that chemical-LTP induced by glycine, which activates NMDARs, increased PSD-93 phosphorylation at Thr612, spine size, and PSD-93 colocalization with PSD-95, while these events were blocked by pretreatment with a Rho-kinase inhibitor. These results indicate that Rho-kinase phosphorylates PSD-93 downstream of NMDARs, and suggest that Rho-kinase mediated phosphorylation of PSD-93 increases the association with PSD-95 and NMDARs to regulate structural synaptic plasticity.

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Effect of NMDA, a Specific Agonist to NMDA Receptor Complex, on Rat Hippocampus

Cited by 7 publications

References 11 publications

Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells treated with MK‑801

Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells treated with MK‑801

Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

Rho-Kinase/ROCK Phosphorylates PSD-93 Downstream of NMDARs to Orchestrate Synaptic Plasticity

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