Selective increase of Nurr1 mRNA expression in mesencephalic dopaminergic neurons of D2 dopamine receptor-deficient mice

Tseng, Kuei Y.; Roubert, Christine; Do, Louis; Rubinstein, Marcelo; Kelly, Michele A.; Grandy, David K.; Low, Malcolm J.; Gershanik, Oscar S.; Murer, Mario Gustavo; Raisman‐Vozari, Rita

doi:10.1016/s0169-328x(00)00107-8

Cited by 19 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data also show the existence of a compensatory mechanism to enhance the impaired DA activity after maternal separation conditions by increasing the expression of Nurr1 protein levels in the VTA. Indeed, Nurr1 is a transcription factor that is essential for the differentiation of midbrain DA neurons [52], and has been reported to be enhanced in the VTA and substance nigra of mice lacking D2R as a compensatory mechanism [53]. Our results also show a negative correlation between Nurr1 expression levels in the VTA, and D2R and DAT expression levels in the NAc of MSEW mice, supporting the role of Nurr1 as a compensatory mechanism when the DA system is downregulated.…”

Section: Discussionmentioning

confidence: 99%

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice

Gracia-Rubio¹,

Martínez-Laorden²,

Moscoso-Castro³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm. The evaluation of neuroplasticity in the striatal dopaminergic pathways revealed that mice exposed to maternal separation exhibited decreased protein expression levels of D2 receptors and increased levels of the transcriptional factor Nurr1. Furthermore, animals exposed to maternal separation and treated with cocaine exhibited increased DA turnover and protein expression levels of DAT and D2R, while decreased Nurr1 and Pitx3 protein expression levels were observed when compared with saline-treated mice. Taken together, our data demonstrate that maternal separation caused an impairment of cocaine-induced behavioural sensitization possibly due to a dysfunction of the dopaminergic system, a dysfunction that has been proposed as a factor of vulnerability for developing substance use disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice

Gracia-Rubio¹,

Martínez-Laorden²,

Moscoso-Castro³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Previous experiments have suggested that antagonism of the D2 receptor is the mechanism through which Nurr1 expression is enhanced in dopamine neurons while stimulation of the D2 receptor can reduce Nurr1 expression. Evidence in support of antagonism of the D2 receptor increasing Nurr1 is first that Nurr1 levels are elevated in D2 receptor knockout mice and second, Nurr1 levels are increased after systemic treatment with D2 receptor antagonists (Tseng et al 2000; Maheux et al 2005). Furthermore, Bannon et al reported reduced Nurr1 expression with cocaine use, a condition that decreases dopamine reuptake which could result in excessive autoreceptor stimulation (Bannon et al 2002).…”

Section: Discussionmentioning

confidence: 99%

NR4A Gene Expression Is Dynamically Regulated in the Ventral Tegmental Area Dopamine Neurons and Is Related to Expression of Dopamine Neurotransmission Genes

et al. 2011

View full text Add to dashboard Cite

The NR4A transcription factors NR4A1, NR4A2, and NR4A3 (also known as Nur77, Nurr1, and Nor1, respectively) share similar DNA-binding properties and have been implicated in regulation of dopamine neurotransmission genes. Our current hypothesis is that NR4A gene expression is regulated by dopamine neuron activity and that induction of NR4A genes will increase expression of dopamine neurotransmission genes. Eticlopride and γ-butyrolactone (GBL) were used in wild-type (+/+) and Nurr1-null heterozygous (+/−) mice to determine the mechanism(s) regulating Nur77 and Nurr1 expression. Laser capture microdissection and real-time PCR was used to measure Nurr1 and Nur77 mRNA levels in the ventral tegmental area (VTA). Nur77 expression was significantly elevated 1 h after both GBL (twofold) and eticlopride (fourfold). In contrast, GBL significantly decreased Nurr1 expression in both genotypes, while eticlopride significantly increased Nurr1 expression only in the +/+ mice. In a separate group of mice, haloperidol injection significantly elevated Nur77 and Nor1, but not Nurr1 mRNA in the VTA within 1 h and significantly increased tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNA expression by 4 h. These data demonstrate that the NR4A genes are dynamically regulated in dopamine neurons with maintenance of Nurr1 expression requiring dopamine neuron activity while both attenuation of dopamine autoreceptors activation and dopamine neuronal activity combining to induce Nur77 expression. Additionally, these data suggest that induction of NR4A genes could regulate TH and DAT expression and ultimately regulate dopamine neurotransmission.

show abstract

“…Interestingly, an age-related decrease of Nurr1 immunoreactivity correlates with decreasing TH expression in the normal process of aging in the human substantia nigra, suggesting a possible regulatory relationship between Nurr1 and TH in the human brain (Chu et al 2002). Nurr1 gene expression is also significantly upregulated in mice lacking functional copies of the DA D2 receptor gene indicating that Nurr1 might mediate autoreceptor functions in mesencephalic DA neurons (Tseng et al 2000). Other genes that are regulated by Nurr1 include the dopamine transporter (DAT) and VMAT2 Sacchetti et al 1999Sacchetti et al , 2001Smits et al 2003).…”

Section: Nurr1 In Developing Da Cellsmentioning

confidence: 99%

Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells

2004

View full text Add to dashboard Cite

Nurr1 is a transcription factor that is expressed in the embryonic ventral midbrain and is critical for the development of dopamine (DA) neurons. It belongs to the conserved family of nuclear receptors but lacks an identified ligand and is therefore referred to as an orphan receptor. Recent structural studies have indicated that Nurr1 belongs to a class of ligand-independent nuclear receptors that are unable to bind cognate ligands. However, Nurr1 can promote signaling via its heterodimerization partner, the retinoid X receptor (RXR). RXR ligands can promote the survival of DA neurons via a process that depends on Nurr1-RXR heterodimers. In developing DA cells, Nurr1 is required for the expression of several genes important for DA synthesis and function. However, Nurr1 is probably also important for the maintenance of adult DA neurons and plays additional less-well-elucidated roles in other regions of the central nervous system and in peripheral tissues.

show abstract

Selective increase of Nurr1 mRNA expression in mesencephalic dopaminergic neurons of D2 dopamine receptor-deficient mice

Cited by 19 publications

References 28 publications

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice

NR4A Gene Expression Is Dynamically Regulated in the Ventral Tegmental Area Dopamine Neurons and Is Related to Expression of Dopamine Neurotransmission Genes

Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells

Contact Info

Product

Resources

About