Phosphorylation of translation initiation factor eIF2α in the brain during pilocarpine-induced status epilepticus in mice

Carnevalli, Larissa S.; Pereira, Cátia M.; Longo, Beatriz M.; Jaqueta, Carolina B.; Avedissian, Marcelo; Mello, Luiz E.; Castilho, Beatriz A.

doi:10.1016/j.neulet.2003.12.093

Cited by 21 publications

(16 citation statements)

References 17 publications

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“…2a), indicating that the increase in eIF2α̣ phosphorylation was specific to CA1 pyramidal cells in our manipulation. Indeed, no obvious eIF2α phosphorylation in the dentate granule cell layer is observed after status epilepticus, during which extensive eIF2α̣ phosphorylation is known to occur in many types of brain cells (Carnevalli et al, 2004). Here, low levels of phospho-eIF2α-IR in the dentate granule cell layer were probably due to the low level of eIF2α expression in this area (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

eIF2α Phosphorylation-Dependent Translation in CA1 Pyramidal Cells Impairs Hippocampal Memory Consolidation without Affecting General Translation

Jiang¹,

Belforte²,

Lü³

et al. 2010

J. Neurosci.

115

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Protein synthesis inhibitor antibiotics are widely used to produce amnesia, and have been recognized to inhibit general or global mRNA translation in the basic translational machinery. For instance, anisomycin interferes with protein synthesis by inhibiting peptidyl transferase or the 80S ribosomal function. Therefore, de novo general or global protein synthesis has been thought to be necessary for long-term memory formation. However, it is unclear which mode of translation-gene-specific translation or general/global translation-is actually crucial for the memory consolidation process in mammalian brains. Here, we generated a conditional transgenic mouse strain in which double-strand RNA-dependent protein kinase (PKR)-mediated phosphorylation of eIF2␣, a key translation initiation protein, was specifically increased in hippocampal CA1 pyramidal cells by the chemical inducer AP20187. Administration of AP20187 significantly increased activating transcription factor 4 (ATF4) translation and concomitantly suppressed CREB-dependent pathways in CA1 cells; this led to impaired hippocampal late-phase LTP and memory consolidation, with no obvious reduction in general translation. Conversely, inhibition of general translation by low-dose anisomycin failed to block hippocampal-dependent memory consolidation. Together, these results indicated that CA1-restricted genetic manipulation of particular mRNA translations is sufficient to impair the consolidation and that consolidation of memories in CA1 pyramidal cells through eIF2␣ dephosphorylation depends more on transcription/translation of particular genes than on overall levels of general translation. The present study sheds light on the critical importance of gene-specific translations for hippocampal memory consolidation.

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Section: Resultsmentioning

confidence: 99%

eIF2α Phosphorylation-Dependent Translation in CA1 Pyramidal Cells Impairs Hippocampal Memory Consolidation without Affecting General Translation

Jiang¹,

Belforte²,

Lü³

et al. 2010

J. Neurosci.

115

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“…Four sections for each region (cingulate gyrus, piriform and primary motor cortex) were mounted on slides for histological evaluation. Histological counting of cells expressing c-Fos protein in the brain regions of interest was performed using the ImageJ® 1.45 s (National Institutes of Health USA) (Carnevali et al, 2004). …”

Section: Methodsmentioning

confidence: 99%

The pattern of c-Fos expression and its refractory period in the brain of rats and monkeys

Barros

Mundim

Galindo

et al. 2015

Front. Cell. Neurosci.

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Intense activation of neurons triggers the appearance of immediate expression genes, including c-Fos. This gene is related to various signal cascades involved in biochemical processes such as neuronal plasticity, cell growth and mitosis. Here we investigate the expression pattern and the refractory period of c-Fos in rats and monkey’s brains after stimulation with pentylenetetrazol. Rats and monkeys were sacrificed at various times after PTZ-induced seizure. Here we show that rats and monkeys already showed c-Fos expression at 0.5 h after seizure. Yet, the pattern of protein expression was longer in monkeys than rats, and also was not uniform (relative intensity) across different brain regions in monkeys as opposed to rats. In addition monkeys had a regional brain variation with regard to the temporal profile of c-Fos expression, which was not seen in rats. The refractory period after a second PTZ stimulation was also markedly different between rats and monkeys with the latter even showing a summatory effect on c-Fos expression after a second stimulation. However, assessment of c-Fos mRNA in rats indicated a post-transcriptional control mechanism underlying the duration of the refractory period. The difference in the protein expression pattern in rodents and primates characterizes a functional aspect of brain biochemistry that differs between these mammalian orders and may contribute for the more developed primate cognitive complexity as compared to rodents given c-Fos involvement in cognitive and learning tasks.

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“…Much of the identified changes during the acute period can also be elicited by compensatory mechanisms corresponding to transcriptionally regulatory as well protein synthesis networks (Carnevalli et al, 2004). The identified protein domains can also suggest the profile of protein families involved in forward changes regarding gene expression and regulation, taking into account the time course development of epilepsy that leads to SRS.…”

Section: Figurementioning

confidence: 99%

Hippocampal gene expression analysis using the ORESTES methodology shows that homer 1a mRNA is upregulated in the acute period of the pilocarpine epilepsy model

et al. 2006

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In the study of temporal lobe epilepsy (TLE) the characterization of genes expressed in the hippocampus is of central importance for understanding their roles in epileptogenic mechanisms. Although several large-scale studies on TLE gene expression have been reported, precise assignment of individual genes associated with this syndrome is still debatable. Here we investigated differentially expressed genes by comparison of mRNAs from normal and epileptic rat hippocampus in the pilocarpine model of epilepsy. For this we used a powerful EST sequencing methodology, ORESTES (Open Reading frame Expressed Sequence Tags), which generates sequence datasets enriched for mRNAs open reading frames (ORFs) rather than simple 5' and 3' ends of mRNAs. Analysis of our sequences shows that ORESTES readily enables the identification of epilepsy associated ORFs. PFAM analysis of protein motifs present in our ORESTES epilepsy database revealed diverse important protein family domains, such as cytoskeletal, cell signaling and protein kinase domains, which could be involved in processes underlying epileptogenesis. More importantly, we show that the expression of homer 1a, known to be coupled to mGluR and NMDA synaptic transmission, is associated with pilocarpine induced status epilepticus (SE). The combined use of the pilocarpine model of epilepsy with the ORESTES technique can significantly contribute to the identification of specific genes and proteins related to TLE. This is the first study applying a large-scale method for rapid shotgun sequencing directed to ORFs in epilepsy research.

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Phosphorylation of translation initiation factor eIF2α in the brain during pilocarpine-induced status epilepticus in mice

Cited by 21 publications

References 17 publications

eIF2α Phosphorylation-Dependent Translation in CA1 Pyramidal Cells Impairs Hippocampal Memory Consolidation without Affecting General Translation

eIF2α Phosphorylation-Dependent Translation in CA1 Pyramidal Cells Impairs Hippocampal Memory Consolidation without Affecting General Translation

The pattern of c-Fos expression and its refractory period in the brain of rats and monkeys

Hippocampal gene expression analysis using the ORESTES methodology shows that homer 1a mRNA is upregulated in the acute period of the pilocarpine epilepsy model

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