Rat nurr1 is prominently expressed in perirhinal cortex, and differentially induced in the hippocampal dentate gyrus by electroconvulsive vs. kindled seizures

Xing, Guoqiang; Zhang, Lixin; Zhang, Lei; Heynen, Terri; Li, Xiuli; Smith, Mark A.; Weiss, Susan R.B.; Feldman, Arron N; Detera‐Wadleigh, Sevilla D.; Chuang, De‐Maw; Post, Robert M.

doi:10.1016/s0169-328x(97)00056-9

Cited by 48 publications

(39 citation statements)

References 78 publications

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“…Several studies have reported that Nr4a1 mRNA is expressed throughout the cerebral cortex (Chan et al 1993;Honkaniemi et al 1995;Xiao et al 1996;Zetterström et al 1996), while Nr4a2 mRNA is not as widespread in the CNS (Saucedo-Cardenas and Conneely 1996;Xiao et al 1996). However, expression of Nr4a2 mRNA in regions associated with memory acquisition and consolidation has been proposed to play a role in memory processing (Xing et al 1997). Our findings support this, showing that following a learning event, expression of NR4A2 protein increased significantly in cortical layer VI.…”

Section: ) (E)supporting

confidence: 86%

Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory

et al. 2012

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Nr4a1 and Nr4a2 are transcription factors and immediate early genes belonging to the nuclear receptor Nr4a family. In this study, we examine their role in long-term memory formation for object location and object recognition. Using siRNA to block expression of either Nr4a1 or Nr4a2, we found that Nr4a2 is necessary for both long-term memory for object location and object recognition. In contrast, Nr4a1 appears to be necessary only for object location. Indeed, their roles in these different types of long-term memory may be dependent on their expression in the brain, as NR4A2 was found to be expressed in hippocampal neurons (associated with object location memory) as well as in the insular and perirhinal cortex (associated with object recognition memory), whereas NR4A1 showed minimal neuronal expression in these cortical areas. These results begin to elucidate how NR4A1 and NR4A2 differentially contribute to object location versus object recognition memory.[Supplemental material is available for this article.]It is well established that long-term memory (LTM) formation requires transcription (for review, see Alberini 2009). Transcription regulated specifically by cAMP responsive element binding protein (CREB) has been shown to be essential for long-term memory (Bourtchuladze et al. 1994;Yin et al. 1994;Guzowski and McGaugh 1997;Pittenger et al. 2002;Sekeres et al. 2010; but see Balschun et al. 2003). Two CREB-dependent immediate early genes that have been implicated in LTM are Nr4a1 and Nr4a2 (Pena de Ortiz et al. 2000; von Hertzen and Giese 2005a,b;Colon-Cesario et al. 2006). Nr4a1 (Nur77) and Nr4a2 (Nurr1) are members of the nuclear steroid/thyroid hormone receptor superfamily that bind in an apparently ligand-independent manner to Nerve Growth Factor1-B (NGFI-B) response elements (Baker et al. 2003;Wang et al. 2003).Expression of both Nr4a1 and Nr4a2 has been shown to increase in the hippocampus following learning. Nr4a1 expression increased in the CA1 region of the hippocampus during context shock memory consolidation, and Nr4a2 increased in CA1 and CA3 pyramidal cell layers of the rat hippocampus following a spatial discrimination task (Pena de Ortiz et al. 2000; von Hertzen and Giese 2005a,b;Keeley et al. 2006;Hawk and Abel 2011). An exception to these findings was a study from Malkani and Rosen (2000) who found increased Nr4a1 expression in the cortex and amygdala following context shock memory consolidation, but failed to see a change in area CA1 of the hippocampus. These patterns of expression suggest a role for the Nr4a family in learning and memory.Transcription of both Nr4a1 and Nr4a2 appear to be regulated by chromatin modification via histone acetylation and deacetylation. Histone deacetylase (HDAC) activity was shown to interfere with formation of the pre-initiation complex at the Nr4a1 promoter, suggesting that acetylation is necessary for its transcription (Fass et al. 2003). In addition, during memory consolidation, the HDAC inhibitor Trichostatin A (TSA) maintained the expression of both Nr4a1 ...

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Section: ) (E)supporting

confidence: 86%

Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory

et al. 2012

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“…Expression of NR4A2 has been described in rat lung (40), and we report responsiveness to cAMP, suggesting a possible role in cell differentiation.…”

Section: Discussionsupporting

confidence: 63%

Gene Induction during Differentiation of Human Pulmonary Type II Cells In Vitro

Wade

Guttentag

Gonzales

et al. 2006

Am J Respir Cell Mol Biol

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Mature alveolar type II cells that produce pulmonary surfactant are essential for adaptation to extrauterine life. We profiled gene expression in human fetal lung epithelial cells cultured in serumfree medium containing dexamethasone and cyclic AMP, a treatment that induces differentiation of type II cells. Microarray analysis identified 388 genes that were induced Ͼ 1.5-fold by 72 h of hormone treatment. Induced genes represented all categories of molecular function and subcellular location, with increased frequency in the categories of ionic channel, cell adhesion, surface film, lysosome, extracellular matrix, and basement membrane. In timecourse experiments, self-organizing map analysis identified a cluster of 17 genes that were slowly but highly induced (5-to ‫ف‬ 190-fold) and represented four functional categories: surfactant-related (SFTPC, SFTPA, PGC, SFTPB, LAMP3, LPL), regulatory (WIF2, IGF2, IL1RL1, NR4A2, HIF3A), metabolic (MAOA, ADH1B, SEPP1), and transport (SCNN1A, CLDN18, AQP4). Induction of both mRNA and protein for these genes, which included nine newly identified regulated genes, was confirmed, and cellular localization was determined in both fetal and postnatal tissue. Induction of lysosomal-associated membrane protein 3 required both hormones, and expression was localized to limiting membranes of lamellar bodies. Hormoneinduced differentiation of human type II cells is associated with genome-wide increased expression of genes with diverse functions. Keywords: cyclic AMP; epithelial differentiation; glucocorticoid; human fetal lung; type II cell Pulmonary type II cells have a number of known physiologic functions. During lung development, they are the progenitor cell for type I cells that constitute the gas exchange surface in alveoli. After lung injury, type II cells proliferate to repopulate the pulmonary epithelium. These cells participate in transepithelial movement of sodium and water to clear fetal lung fluid at birth and to maintain alveolar fluid homeostasis with air breathing. Type II cells produce a variety of cytokines, chemokines, and other proteins involved in the inflammatory response, as well as proteins that have either immunomodulary or antioxidant roles. The most specialized function of type II cells is the production and secretion of surfactant, the complex mixture of lipid and surfactant proteins (SPs) that maintains alveolar stability and is required for successful adaptation to extrauterine life (1-3). Differentiation of type II cells from undifferentiated precursor epithelial cells is marked by the disappearance of glycogen, which serves as a substrate for surfactant phospholipid synthesis, the formation of lamellar bodies, which are the intracellular storage sites for secreted surfactant, and expansion of the apical cell surface in the form of microvilli (4-7). A number of classes of proteins are developmentally increased during type II cell differentiation, including SPs, lipogenic enzymes, selected water and ion transporter/channels, metabolic enzymes, and structural p...

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“…The NGFI-B/Nurr1/Nor1 group of receptors are rapidly induced in the CNS after stressful insults such as kainic acid-induced seizures, for example (9,10,12). Thus, an exciting hypothesis is that the function of stress-induced NGFI-B/Nurr1/Nor1 gene expression in post-mitotic neurons could be related to the growth inhibitory properties of these receptors and serve to stabilize the non-proliferative state after stressful insults.…”

Section: Vp16mentioning

confidence: 99%

Induction of Cell Cycle Arrest and Morphological Differentiation by Nurr1 and Retinoids in Dopamine MN9D Cells

Castro¹,

Hermanson²,

Joseph³

et al. 2001

Journal of Biological Chemistry

113

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Dopamine cells are generated in the ventral midbrain during embryonic development. The progressive degeneration of these cells in patients with Parkinson's disease, and the potential therapeutic benefit by transplantation of in vitro generated dopamine cells, has triggered intense interest in understanding the process whereby these cells develop. Nurr1 is an orphan nuclear receptor essential for the development of midbrain dopaminergic neurons. However, the mechanism by which Nurr1 promotes dopamine cell differentiation has remained unknown. In this study we have used a dopamine-synthesizing cell line (MN9D) with immature characteristics to analyze the function of Nurr1 in dopamine cell development. The results demonstrate that Nurr1 can induce cell cycle arrest and a highly differentiated cell morphology in these cells. These two functions were both mediated through a DNA binding-dependent mechanism that did not require Nurr1 interaction with the heterodimerization partner retinoid X receptor. However, retinoids can promote the differentiation of MN9D cells independently of Nurr1. Importantly, the closely related orphan receptors NGFI-B and Nor1 were also able to induce cell cycle arrest and differentiation. Thus, the growth inhibitory activities of the NGFI-B/Nurr1/ Nor1 orphan receptors, along with their widespread expression patterns both during development and in the adult, suggest a more general role in control of cell proliferation in the developing embryo and in adult tissues.

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Rat nurr1 is prominently expressed in perirhinal cortex, and differentially induced in the hippocampal dentate gyrus by electroconvulsive vs. kindled seizures

Cited by 48 publications

References 78 publications

Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory

Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory

Gene Induction during Differentiation of Human Pulmonary Type II Cells In Vitro

Induction of Cell Cycle Arrest and Morphological Differentiation by Nurr1 and Retinoids in Dopamine MN9D Cells

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