Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B

Priya, Anusha; Johar, Kaid; Wong‐Riley, Margaret T.T.

doi:10.1016/j.bbamcr.2013.07.002

Cited by 28 publications

(39 citation statements)

References 45 publications

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“…When incubated with mouse visual cortical tissue nuclear extract, GM3 synthase formed specific DNA/Sp3 and DNA/Sp4 shift and supershift complexes (Figure 1, lane 1 for Sp3/Sp4 shift, lanes 4 and 5 for Sp3 and Sp4 supershift, respectively) but did not form a DNA/Sp1 shift or supershift complex (Figure 1, lanes 1 and 3 respectively). The lack of a strong Sp4 supershift with HeLa nuclear extract as compared to mouse visual cortical nuclear extract is consistent with our previous observations of different levels of Sp4 abundance in the two nuclear extracts and with its reported neuronal distribution [19, 28]. Similarly, the lack of Sp1 shift or supershift with mouse cortical nuclear extract as compared to HeLa nuclear extract was due to the lower abundance of Sp1 in mouse cortical nuclear extract as compared to HeLa nuclear extract [28].…”

Section: Resultssupporting

confidence: 92%

“…The lack of a strong Sp4 supershift with HeLa nuclear extract as compared to mouse visual cortical nuclear extract is consistent with our previous observations of different levels of Sp4 abundance in the two nuclear extracts and with its reported neuronal distribution [19, 28]. Similarly, the lack of Sp1 shift or supershift with mouse cortical nuclear extract as compared to HeLa nuclear extract was due to the lower abundance of Sp1 in mouse cortical nuclear extract as compared to HeLa nuclear extract [28]. The shift bands for visual cortical and HeLa nuclear extract were competed out with the addition of cold competitors (Figure 1, lanes 2 and 7, respectively).…”

Section: Resultssupporting

confidence: 92%

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Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2)

Priya

Johar

Nair

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are important glutamatergic receptors mediating fast excitatory synaptic transmission in the brain. The regulation of the four subunits of AMPA receptors, GluA1-4, is poorly understood. Excitatory synaptic transmission is highly energy-demanding, and this energy is derived mainly from the oxidative pathway. Recently, we found that specificity factor regulates all subunits of cytochrome c oxidase (COX), a critical energy-generating enzyme. COX is also regulated by nuclear respiratory factor 1 (NRF-1), which transcriptionally controls the Gria2 (GluA2) gene of AMPA receptors. The goal of the present study was to test our hypothesis that Sp-factors (Sp1, Sp3, and/or Sp4) also regulate AMPA subunit genes. If so, we wish to determine if Sp-factors and NRF-1 function via a complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel mechanism. By means of multiple approaches, including electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutations, real-time quantitative PCR, and western blot analysis, we found that Sp4, but not Sp1 or Sp3, regulates the Gria2, but not Gria 1, 3, or 4, subunit gene of the AMPA receptor in a concurrent and parallel manner with NRF-1. Thus, Sp4 and NRF-1 both mediate the tight coupling between neuronal activity and energy metabolism at the transcriptional level.

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Section: Resultssupporting

confidence: 92%

Section: Resultssupporting

confidence: 92%

Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2)

Priya

Johar

Nair

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Furthermore, the mechanism(s) underlying impaired motivation and learning resulting from reduced Sp4 expression have yet to be delineated. As SP4 regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B (Priya et al, 2014;Priya et al, 2013), further investigation of other mechanisms using these mice is warranted.…”

Section: Discussionmentioning

confidence: 99%

GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders

Young

Kamenski

Higa

et al. 2015

Neuropsychopharmacol

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Serious mental illness occurs in 25% of the general population, with many disorders being neurodevelopmental, lifelong, and debilitating. The wide variation and overlap in symptoms across disorders increases the difficulty of research and treatment development. The NIMH Research Domain of Criteria initiative aims to improve our understanding of the molecular and behavioral consequences of specific neurodevelopmental mechanisms across disorders, enabling targeted treatment development. The transcription factor Specificity Protein 4 (SP4) is important for neurodevelopment and is genetically associated with both schizophrenia and bipolar disorder. Reduced Sp4 expression in mice (hypomorphic) reproduces several characteristics of psychiatric disorders. We further tested the utility of Sp4 hypomorphic mice as a model organism relevant to psychiatric disorders by assessing cognitive control plus effort and decision-making aspects of approach motivation using cross-species-relevant tests. Sp4 hypomorphic mice exhibited impaired attention as measured by the 5-Choice Continuous Performance Test, an effect that was attenuated by glycine type-1 transporter (GlyT-1) inhibition. Hypomorphic mice also exhibited reduced motivation to work for a reward and impaired probabilistic learning. These deficits may stem from affected anticipatory reward, analogous to anhedonia in patients with schizophrenia and other psychiatric disorders. Neither positive valence deficit was attenuated by GlyT-1 treatment, suggesting that these and the attentional deficits stem from different underlying mechanisms. Given the association of SP4 gene with schizophrenia and bipolar disorder, the present studies provide support that personalized GlyT-1 inhibition may treat attentional deficits in neuropsychiatric patients with low SP4 levels.

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“…It has been reported that for many genes, transcript and protein levels do not correlate well (Tian et al 2004). However, there are some reports that transcript levels of the GluN1 subunit are correlate with its protein levels (Jayanthi Priya et al 2013). In addition, it has been recently reported that complete deletion of the obligatory GluN1 subunit of the NMDA receptors in hippocampal slice cultures completely eliminates NMDA receptors (Incontro et al 2014).…”

Section: Days After Bdlmentioning

confidence: 97%

Hepatic encephalopathy induces site-specific changes in gene expression of GluN1 subunit of NMDA receptor in rat brain

2015

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We investigate changes in gene expression of GluN1 subunit of N-Methyl-D-Aspartate (NMDA) receptor in the prefrontal cortex (PFC), hippocampus and striatum in a rat model of hepatic encephalopathy (HE). We used male Wistar rats in which HE was induced after a common bile duct ligation (BDL). The animals were divided into three sets, and each set included three groups of control, sham operated and BDL. In the first set of animals, blood samples collected for biochemical analysis on day 21 of BDL. In the second set, changes in nociception threshold was assessed on day 21 of BDL using a hotplate test. In the third set, whole brain extracted, and the PFC, the hippocampus and the striatum in each rat were immediately dissected. We used a semi-quantitative RT-PCR method for evaluating the GluN1 gene expression. The biochemical analyses showed that plasma levels of ammonia and bilirubin in BDL rats were significantly increased compared to the sham control group on day 21 of BDL (P < 0.01). Nociception threshold was also increased in rats with BDL compared to sham group (P < 0.001). The results revealed that the GluN1 gene expression at mRNA levels in BDL group was decreased by 19 % in the PFC (P < 0.05) but increased by 82 % in the hippocampus (P < 0.01) compared to the sham control group; however, no significant change was observed in the striatum. It can be concluded that HE affects the GluN1 gene expression in rat brain with a site-specific pattern, and the PFC and hippocampus are more sensitive areas than striatum.

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Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B

Cited by 28 publications

References 45 publications

Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2)

Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2)

GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders

Hepatic encephalopathy induces site-specific changes in gene expression of GluN1 subunit of NMDA receptor in rat brain

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