Early modifications in N-methyl-d-aspartate receptor subunit mRNA levels in an oxygen and glucose deprivation model using rat hippocampal brain slices

Dos-Anjos, Severiano; Martínez-Villayandre, Beatriz; Montori, Sheyla; Pérez-García, Carlos César; Fernández‐López, Arsenio

doi:10.1016/j.neuroscience.2009.09.019

Cited by 15 publications

(13 citation statements)

References 29 publications

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“…Furthermore, we found that the subunit composition of NMDARs is altered after the OGD insult, which is in agreement with previous studies showing a down-regulation of genes encoding for subunits of the NMDARs after in vivo [6], [62]–[64] and in vitro [13], [65] ischemia. In our experimental system, OGD decreased the total mRNA and protein levels of the GluN2 subunits without affecting the protein levels of the GluN1 subunit ( Figure 9 ).…”

Section: Discussionsupporting

confidence: 93%

In Vitro Ischemia Triggers a Transcriptional Response to Down-Regulate Synaptic Proteins in Hippocampal Neurons

et al. 2014

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Transient global cerebral ischemia induces profound changes in the transcriptome of brain cells, which is partially associated with the induction or repression of genes that influence the ischemic response. However, the mechanisms responsible for the selective vulnerability of hippocampal neurons to global ischemia remain to be clarified. To identify molecular changes elicited by ischemic insults, we subjected hippocampal primary cultures to oxygen-glucose deprivation (OGD), an in vitro model for global ischemia that resulted in delayed neuronal death with an excitotoxic component. To investigate changes in the transcriptome of hippocampal neurons submitted to OGD, total RNA was extracted at early (7 h) and delayed (24 h) time points after OGD and used in a whole-genome RNA microarray. We observed that at 7 h after OGD there was a general repression of genes, whereas at 24 h there was a general induction of gene expression. Genes related with functions such as transcription and RNA biosynthesis were highly regulated at both periods of incubation after OGD, confirming that the response to ischemia is a dynamic and coordinated process. Our analysis showed that genes for synaptic proteins, such as those encoding for PICK1, GRIP1, TARPγ3, calsyntenin-2/3, SAPAP2 and SNAP-25, were down-regulated after OGD. Additionally, OGD decreased the mRNA and protein expression levels of the GluA1 AMPA receptor subunit as well as the GluN2A and GluN2B subunits of NMDA receptors, but increased the mRNA expression of the GluN3A subunit, thus altering the composition of ionotropic glutamate receptors in hippocampal neurons. Together, our results present the expression profile elicited by in vitro ischemia in hippocampal neurons, and indicate that OGD activates a transcriptional program leading to down-regulation in the expression of genes coding for synaptic proteins, suggesting that the synaptic proteome may change after ischemia.

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Section: Discussionsupporting

confidence: 93%

In Vitro Ischemia Triggers a Transcriptional Response to Down-Regulate Synaptic Proteins in Hippocampal Neurons

et al. 2014

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“…This effect has been previously reported in an ex vivo model of hippocampal slices, where decreases in some glutamatergic gene mRNA levels (GluN1, GluN2A and GluN2B) induced by OGD can be reverted by NMDA antagonists (Dos-Anjos et al, 2009). The increase of transcript amounts in some genes (i.e.…”

Section: Discussionsupporting

confidence: 78%

“…Our study indicates that treatment with meloxicam prevents cell mortality while promotes significant increases of the NMDA and AMPA receptor subunit transcript levels, previously reduced by the OGD injury. These effects seem to be contradictory since a general transcript decrease of the glutamatergic receptor subunit has been suggested to be responsible for neuroprotection following ischemia (Dos-Anjos et al, 2009). Then, how can the meloxicam elicit neuroprotection and at the same time increase the NMDA and AMPA receptor subunit transcripts?…”

Section: Discussionmentioning

confidence: 99%

Glutamate receptor and transporter modifications in rat organotypic hippocampal slice cultures exposed to oxygen–glucose deprivation: The contribution of cyclooxygenase-2

Llorente

Landucci

Pellegrini‐Giampietro

et al. 2015

Neuroscience

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“…According to a previous report, mGluR5 mRNA decreased significantly in ischemic preconditioning group compared to the non-preconditioning group [35]. In addition, in a previous in vitro study it was suggested that the mechanism of down-regulating NMDAR subunits mRNA levels by oxygen/glucose deprivation or glutamate receptor antagonists could be identical [36]. In the present study, the difference between the non-exercise group and sham group is whether the middle cerebral artery is occluded.…”

Section: Resultsmentioning

confidence: 52%

The Effect of Treadmill Training Pre-Exercise on Glutamate Receptor Expression in Rats after Cerebral Ischemia

Zhang

Jia

et al. 2010

IJMS

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Physical exercise has been demonstrated to be neuroprotective in both clinical and laboratory settings. However, the exact mechanism underlying this effect is unclear. Our study aimed to investigate whether pre-ischemic treadmill training could serve as a form of ischemic preconditioning in a rat model undergoing middle cerebral artery occlusion (MCAO). Thirty-six rats were divided into three groups: a sham control group, a non-exercise with operation group and an exercise with operation group. After treadmill training, ischemia was induced by occluding the MCA for 2 h, followed by reperfusion. Half of the rats in each group were sacrificed for mRNA detection of mGluR5 and NR2B 80 min after occlusion. The remaining animals were evaluated for neurological deficits by behavioral scoring and then decapitated to assess the infarct volume. The mRNA expression of mGluR5 and NR2B was detected by real-time PCR. The results suggest that pre-ischemic treadmill training may induce brain ischemic tolerance by reducing the mRNA levels of mGluR5 and NR2B, and thus, the results indicate that physical exercise might be an effective method to establish ischemic preconditioning.

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Early modifications in N-methyl-d-aspartate receptor subunit mRNA levels in an oxygen and glucose deprivation model using rat hippocampal brain slices

Cited by 15 publications

References 29 publications

In Vitro Ischemia Triggers a Transcriptional Response to Down-Regulate Synaptic Proteins in Hippocampal Neurons

In Vitro Ischemia Triggers a Transcriptional Response to Down-Regulate Synaptic Proteins in Hippocampal Neurons

Glutamate receptor and transporter modifications in rat organotypic hippocampal slice cultures exposed to oxygen–glucose deprivation: The contribution of cyclooxygenase-2

The Effect of Treadmill Training Pre-Exercise on Glutamate Receptor Expression in Rats after Cerebral Ischemia

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