scholarly journals Gene regulation by NMDA receptor activation in the SDN-POA neurons of male rats during sexual development

2005 ◽  
Vol 34 (2) ◽  
pp. 433-445 ◽  
Author(s):  
Hseng-Kuang Hsu ◽  
Pei-Lin Shao ◽  
Ke-Li Tsai ◽  
Huei-Chuan Shih ◽  
Tzu-Ying Lee ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Cytochrome Oxidase ◽  
Sexual Development ◽  
Neuronal Apoptosis ◽  
Receptor Activation ◽  
Binding Activity ◽  
Male Rats ◽  
Cytochrome Oxidase Subunit ◽  
Mk 801 ◽  
Nmda Receptor Activation

The present study was designed to identify possible signaling pathways, which may play a role in prevention of neuronal apoptosis in the sexually dimorphic nucleus of the preoptic area (SDN-POA) after physiological activation of the N-methyl-D-aspartate (NMDA) receptor. Gene response to the blockage of the NMDA receptor by an antagonist (dizocilpine hydrogen maleate; MK-801) was screened after suppression subtractive hybridization (SSH). The results showed that dfferential screening after SSH detected the presence of some neurotrophic genes (RNA binding motif protein 3 (RBM3), α-tubulin) as well as apoptosis-related genes (Bcl-2, cytochrome oxidase subunit II, cytochrome oxidase subunit III) in the SDN-POA of male rats, which were down-regulated by blocking the NMDA receptor. The RT-PCR products of the aforementioned genes in MK-801-treated males were significantly less than that in untreated males. In particular, the expression of Bcl-2 mRNA, including Bcl-2 protein, in male rats were significantly suppressed by MK-801 treatment. Moreover, the binding activity of nuclear factor κB (NFκB) was significantly higher in male rats than in females, but significantly diminished by blocking the NMDA receptor with MK-801 in male rats. No significant difference in cAMP response element-binding protein (CREB) binding activity was observed among untreated male, MK-801-treated male, untreated female and MK-801-treated female groups. These results suggest that genes regulated by NMDA receptor activation might participate in neuronal growth and/or anti-apoptosis, and support an important signaling pathway of NFκB activation and its target gene, Bcl-2, in preventing neuronal apoptosis in the SDN-POA of male rats during sexual development.

scholarly journals Increase in External Glutamate and NMDA Receptor Activation Contribute to H2O2-Induced Neuronal Apoptosis

2001 ◽  
Vol 73 (3) ◽  
pp. 1181-1188 ◽  
Author(s):  
Franck Mailly ◽  
Philippe Marin ◽  
Maurice Israël ◽  
Jacques Glowinski ◽  
Joël Prémont
Keyword(s):  
Nmda Receptor ◽  
Neuronal Apoptosis ◽  
Receptor Activation ◽  
Nmda Receptor Activation

Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease

2006 ◽  
Vol 21 (2) ◽  
pp. 392-403 ◽  
Author(s):  
Jacqueline Shehadeh ◽  
Herman B. Fernandes ◽  
Melinda M. Zeron Mullins ◽  
Rona K. Graham ◽  
Blair R. Leavitt ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Huntington Disease ◽  
Neuronal Apoptosis ◽  
Receptor Activation ◽  
Transgenic Mouse Model ◽  
Nmda Receptor Activation

scholarly journals Spinal NMDA receptor activation is necessary for de novo, but not the maintenance of, A2a receptor-mediated phrenic motor facilitation

2009 ◽  
Vol 107 (1) ◽  
pp. 217-223 ◽  
Author(s):  
F. J. Golder
Keyword(s):  
Nmda Receptor ◽  
Phrenic Nerve ◽  
De Novo ◽  
Receptor Activation ◽  
Nerve Activity ◽  
Mk 801 ◽  
Phrenic Nerve Activity ◽  
Cgs 21680 ◽  
A2a Receptor ◽  
Nmda Receptor Activation

Adenosine 2a (A2a) receptor agonists elicit persistent increases in phrenic nerve activity by transactivating the neurotrophin receptor, TrkB, near phrenic motoneurons. Our working model proposes that A2a receptor-mediated TrkB receptor activation strengthens glutamatergic synapses onto phrenic motoneurons. Activation of glutamate N-methyl d-aspartate (NMDA) receptors has been implicated in other models of phrenic motor plasticity. Thus we hypothesized that NMDA receptor activation also would contribute to A2a receptor-mediated phrenic motor facilitation. Adult male Sprague-Dawley rats were anesthetized with urethane, mechanically ventilated, neuromuscularly paralyzed, and bilaterally vagotomized. The A2a receptor agonist CGS-21680 and the NMDA receptor-channel blocker MK-801 were administered intrathecally over the C4 spinal segment. Phrenic nerve activity was recorded before, during, and after drug administration. MK-801 (concentration range 0.1, 1.0, 10.0, and 100 μM) was administered 30 min before CGS-21680 (50 μM). MK-801 dose-dependently blocked A2a receptor-mediated phrenic motor facilitation. When administered at 60 min post-CGS-21680, MK-801 prevented further increases in phrenic nerve activity compared with the CGS-21680 alone (CGS-21680 alone at 120 min: 114 ± 19%; CGS-21680 and MK-801 at 60 min post-CGS-21680: 61 ± 11%, above baseline, P < 0.05) but did not return phrenic motor output to baseline values. Our data suggest that NMDA receptor activation is necessary for de novo A2a receptor-mediated phrenic motor facilitation and that the maintenance of preexisting phrenic motor facilitation does not involve NMDA receptor-dependent mechanisms.

123Iodo-MK-801: A spect agent for imaging the pattern and extent of glutamate (NMDA) receptor activation in Alzheimer's disease

1997 ◽  
Vol 31 (6) ◽  
pp. 605-619 ◽  
Author(s):  
Derek R.P. Brown ◽  
David J. Wyper ◽  
Jonathan Owens ◽  
James Patterson ◽  
R. Ciara Kelly ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nmda Receptor ◽  
Receptor Activation ◽  
Mk 801 ◽  
Nmda Receptor Activation

NF-κB induction during in vivo hypoxia in dorsocaudal brain stem of rat: effect of MK-801 andl-NAME

1998 ◽  
Vol 85 (1) ◽  
pp. 372-376 ◽  
Author(s):  
Evelyne Gozal ◽  
Narong Simakajornboon ◽  
David Gozal
Keyword(s):  
Nmda Receptor ◽  
Brain Stem ◽  
Receptor Activation ◽  
Hypoxic Ventilatory Response ◽  
Mk 801 ◽  
Oxide Synthase ◽  
Nmda Receptor Channel ◽  
Nmda Receptor Activation ◽  
Receptor Channel

In the nucleus of the solitary tract, NMDA receptors are critical for the hypoxic ventilatory response while neuronal nitric oxide synthase (NOS) modulates the late component of this response. Nuclear factor (NF)-κB is a ubiquitous transcription factor that increases the expression of multiple stress-activated genes. We sought to examine temporal changes in expression of NF-κB within the dorsocaudal brain stem of conscious rats after exposures to 10% O2. Time-dependent increases in NF-κB occurred with hypoxia and peaked at 60 min. Pretreatment with the N-methyl-d-aspartate (NMDA)-receptor channel antagonist dizocilpine maleate (MK-801) markedly attenuated NF-κB complexes during hypoxia. In contrast, after NOS inhibition with N G-nitro-l-arginine methyl ester (l-NAME), although NF-κB was diminished in normoxia, increased NF-κB expression still occurred with hypoxia. Increased phosphorylation of the NF-κB regulatory unit [inhibitory (I)κB] was detected by immunoblotting and also peaked at 60 min. Phosphorylation of Iκ-B during hypoxia was attenuated by MK-801 but not byl-NAME. Thus NMDA-receptor activation in the dorsocaudal brain stem during hypoxia elicits in NF-κB activity marked enhancements that are unaffected after NOS blockade.

Prenatal Exposure of Testosterone Prevents SDN-POA Neurons of Postnatal Male Rats From Apoptosis Through NMDA Receptor

2001 ◽  
Vol 86 (5) ◽  
pp. 2374-2380 ◽  
Author(s):  
Hseng-Kuang Hsu ◽  
Rei-Cheng Yang ◽  
Huei-Chuan Shih ◽  
Ya-Lun Hsieh ◽  
U-Yang Chen ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Testosterone Level ◽  
Neuronal Apoptosis ◽  
Preoptic Area ◽  
Receptor Expression ◽  
Female Rats ◽  
Male Rats ◽  
Intact Male ◽  
Mk 801 ◽  
Subunit Protein

The role of N-methyl-d-aspartate (NMDA) receptor in mediating the effect of testosterone exposure prenatally on neuronal apoptosis in the sexual dimorphic nucleus of the preoptic area (SDN-POA) of rats was studied. The endogenous testosterone was diminished by prenatal stress (PNS) or simulated by testosterone exposure (TE) to understand the effect of testosterone on NR1 (a functional subunit protein of NMDA receptor) expression and neuronal apoptosis. To further study whether the testosterone, after being converted into estradiol, modulates NR1 expression, 4-androstein-4-ol-3,17-dione (ATD; an aromatase inhibitor) was used to block the conversion of estradiol from testosterone. The expressions of the NR1 mRNA and NR1 subunit protein were quantified by RT-PCR and western blotting analysis, respectively. In addition, a noncompetitive antagonist of NMDA receptor, MK-801, was used to find out whether blockage of NMDA receptor affects the naturally occurring apoptosis in SDN-POA. The results showed the following. 1) Expression of perinatal NR1 subunit protein in the central part of the medial preoptic area of male rats was significantly higher than that of females, especially on postnatal days 1 and 3. 2) The testosterone level of male fetuses on embryonic day 18 was significantly higher than that of females, while the testosterone level of TE females or PNS males was similar to that of intact males or intact females, respectively. 3) The apoptotic incidence of intact male rats was significantly less than that of females, and the apoptosis was stimulated by PNS in male or inhibited by TE in female. 4) The expression of NR1 subunit protein could be inhibited by PNS or ATD-treatment in male, while stimulated by TE in female. 5) NR1 mRNA showed no significant difference among intact male, PNS male, ATD-treated male, TE female and intact female rats. 6) The low apoptotic incidence of male rats was significantly increased when NMDA receptor was blocked by MK-801. These results suggest that testosterone, after being converted to estradiol, may prevent the SDN-POA neurons of male rats from apoptosis through enhancing the expression of NR1 at the posttranscriptional level.

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