Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

DeSteno, Deirdre A.; Schmauss, Claudia

doi:10.1016/j.neuroscience.2008.01.012

Cited by 58 publications

(58 citation statements)

References 40 publications

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“…Since having similar protein structure, Egr2 maybe shares similar function with Egr1. In fact, memory recall is accompanied by increased Egr2 mRNA expression, specific role of Egr2-mediated transcriptional activation in cognitive functions associates with attention (DeSteno and Schmauss 2008). In the present study, cerebral ischemia-reperfusion caused down-expression of Egr2 with impaired memory and cognitive function, and GO analysis showed Egr2 associated with myelination, Schwann cell differentiation, brain segmentation and other biological process, consistent with the previous report (DeSteno and Schmauss 2008).…”

Section: Discussionsupporting

confidence: 91%

Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia

Feng

et al. 2015

Tohoku J. Exp. Med.

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Vascular dementia (VD) has been one of the most serious public health problems worldwide. It is well known that cerebral hypoperfusion is the key pathophysiological basis of VD, but it remains unclear how global genes in hippocampus respond to cerebral ischemia-reperfusion. In this study, we aimed to reveal the global gene expression profile in the hippocampus of VD using a rat model. VD was induced by repeated occlusion of common carotid arteries followed by reperfusion. The rats with VD were characterized by deficit of memory and cognitive function and by the histopathological changes in the hippocampus, such as a reduction in the number and the size of neurons accompanied by an increase in intercellular space. Microarray analysis of global genes displayed up-regulation of 7 probesets with genes with fold change more than 1.5 (P < 0.05) and down-regulation of 13 probesets with genes with fold change less than 0.667 (P < 0.05) in the hippocampus. Gene Ontology (GO) and pathway analysis showed that the up-regulated genes are mainly involved in oxygen binding and transport, autoimmune response and inflammation, and that the down-regulated genes are related to glucose metabolism, autoimmune response and inflammation, and other biological process, related to memory and cognitive function. Thus, the abnormally expressed genes are closely related to oxygen transport, glucose metabolism, and autoimmune response. The current findings display global gene expression profile of the hippocampus in a rat model of VD, providing new insights into the molecular pathogenesis of VD.

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Section: Discussionsupporting

confidence: 91%

Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia

Feng

et al. 2015

Tohoku J. Exp. Med.

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“…Egr2 is induced by neuronal activity (29), but less is known about its specific role. However, Egr2 was clearly shown to mediate stabilization and maintenance of LTP (32,33) and cognitive functions associated with attention (34) in models in which Egr1 was induced only transiently (33) or was not induced (34). Therefore, different members of the Egr family might mediate different cognitive functions associated with neuronal plasticity.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin-induced changes in brain gene expression reveal induction of synaptic plasticity genes in experimental stroke

Mengozzi

Cervellini

Villa

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Erythropoietin (EPO) is a neuroprotective cytokine in models of ischemic and nervous system injury, where it reduces neuronal apoptosis and inflammatory cytokines and increases neurogenesis and angiogenesis. EPO also improves cognition in healthy volunteers and schizophrenic patients. We studied the effect of EPO administration on the gene-expression profile in the ischemic cortex of rats after cerebral ischemia at early time points (2 and 6 h). EPO treatment up-regulated genes already increased by ischemia. Hierarchical clustering and analysis of overrepresented functional categories identified genes implicated in synaptic plasticity-Arc, BDNF, Egr1, and Egr2, of which Egr2 was the most significantly regulated. Up-regulation of Arc, BDNF, Dusp5, Egr1, Egr2, Egr4, and Nr4a3 was confirmed by quantitative PCR. We investigated the up-regulation of Egr2/Krox20 further because of its role in neuronal plasticity. Its elevation by EPO was confirmed in an independent in vivo experiment of cerebral ischemia in rats. Using the rat neuroblastoma B104, we found that wild-type cells that do not express EPO receptor (EPOR) do not respond to EPO by inducing Egr2. However, EPOR-expressing B104 cells induce Egr2 early upon incubation with EPO, indicating that Egr2 induction is a direct effect of EPO and that EPOR mediates this effect. Because these changes occur in vivo before decreased inflammatory cytokines or neuronal apoptosis is evident, these findings provide a molecular mechanism for the neuroreparative effects of cytokines and suggest a mechanism of neuroprotection by which promotion of a plastic phenotype results in decreased inflammation and neuronal death.microarrays | ischemia-reperfusion injury | neurotrophins | early genes | neuronal cells S ince our first report (1), several studies have documented the neuroprotective effect of erythropoietin (EPO) in models of ischemic and traumatic brain injury (reviewed in refs. 2-4) and the role of endogenous EPO in ischemic preconditioning (5). Multiple mechanisms can account for the action of EPO, including inhibition of neuronal apoptosis (6) and decreased neuroinflammation (7,8). EPO also activates repair, in particular through promotion of neurogenesis, oligodendrogenesis, and angiogenesis (9, 10), as well as mobilization of endothelial progenitor cells (11). It also improves cognition, long-term potentiation (LTP), and synaptic plasticity (4,(12)(13)(14).However, the early effects of EPO responsible for its neuroprotective activities are not understood, and there even is debate whether the classical EPO receptor (EPOR) alone mediates these effects or an additional tissue-protective coreceptor is required (15-18).In the study presented here, we investigated the effect of EPO on the gene-expression profile of the brain using the rat model of cerebral ischemia induced by middle cerebral artery occlusion (MCAO) with which we performed most of the studies on EPO.To identify early events induced by EPO, experiments were carried out at the time points 2 and 6 h post-MCAO, when ...

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“…Induction of the egr-1 depends on neuronal activity and is thought to be involved in neuronal plasticity (Cole et al 1989), learning and memory (e.g. Hall et al 2001, Bozon et al 2003, while the level of egr-2 expression in the prefrontal cortex (OFC and mPFC) was found to correlate with the magnitude of cognitive control involved in the task performance (DeSteno and Schmauss 2008). Beside the DAT mutant mice, we also examined the mice withdrawn from the treatment with the potent and selective DAT inhibitor, GBR 12909 (Heikkila and Manzino 1984).…”

Section: Introductionmentioning

confidence: 99%

Potential role of dopamine transporter in behavioral flexibility

Cybulska-Kłosowicz¹,

Dąbrowska²,

Niedzielec³

et al. 2017

Acta Neurobiologiae Experimentalis

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Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes. Here we used a gene knockout mouse model to investigate the role of DAT in the performance on the Attentional Set-Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally, behavior of mice after repeated administration of selective DAT inhibitor, GBR 12909, was examined.The animals were treated with the inhibitor to elicit a compensatory DAT up-regulation following withdrawal. Learning was slower and the number of errors during reversal learning and intra-dimensional shift stages was higher in DAT+/− mutant mice than in WT mice. GBR 12909-treated mice had deficits in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the ASST was examined with early growth response proteins 1 and 2 (egr-1, egr-2) immunohistochemistry. Density of egr-2 labeled cells in the OFC was lower in mutant mice than in wild-types during reversal learning and the expression of the egr-1 was lower in mutant mice in the OFC and DMS during reversal and intra-dimensional shift stages. Mice with decreased DAT levels displayed behavioral difficulties that were accompanied by a lower task-induced activation of neurons in brain regions involved in the reversal learning. Altogether, these data indicate the role of the DAT in the behavioral flexibility.

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Induction of early growth response gene 2 expression in the forebrain of mice performing an attention-set-shifting task

Cited by 58 publications

References 40 publications

Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia

Global Gene Expression Profile of the Hippocampus in a Rat Model of Vascular Dementia

Erythropoietin-induced changes in brain gene expression reveal induction of synaptic plasticity genes in experimental stroke

Potential role of dopamine transporter in behavioral flexibility

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