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Differential Regulation of GLT-1/EAAT2 Gene Expression by NF-κB and N-myc in Male Mouse Brain During Postnatal Development

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Abstract

The synaptic glutamate level homeostasis is mainly maintained by the astrocytes membrane bound glutamate transporter type-1 (GLT-1/EAAT2). Alterations in its expression during development and aging and the underlying mechanisms are not well studied. Here, we report that NF-κB interaction was highest in both cerebral and cerebellar cortices at day 15 when compared with that at day 0 during development, and it further declined significantly in day 45, and remained unchanged in 20 and 70 weeks mice. On the other hand, N-myc interaction was highest at 0 day which significantly declined at 15-day and interestingly remained unaltered at later ages in both the cortices. This age dependent reciprocal pattern of NF-κB and N-myc interactions with their cognate GLT-1 promoter sequences was further correlated with GLT-1 protein and transcript levels. We found that higher NF-κB interaction with its cognate GLT-1 promoter sequences correlates with up-regulation whereas the higher N-myc interaction correlates with down-regulation of GLT-1 expression during postnatal developmental age up to 15 day, however, such phenomenon was not found in the higher ages from day 45 to 70 weeks. Thus our data suggests a postnatal development- and age dependent differential interaction of transcription factors NF-κB and N-myc to their respective sequences and they act as positive and negative regulator, respectively of GLT-1 gene expression in the brain during early developmental period in both cerebral and cerebellar cortices which might be different in aging of mice.

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Acknowledgments

R.K.G. thanks CSIR for Junior and Senior Research Fellowships (File No: 09/013 (0111) 2007-EMR I). Financial assistance from CSIR (37/1389/09/EMR-II) and BRNS (2009/37/55/3298), Govt. of India to SP is gratefully acknowledged.

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  1. Molecular Biology and Biochemistry Lab., Centre of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Rajaneesh Kumar Gupta & S. Prasad

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  1. Rajaneesh Kumar Gupta
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  2. S. Prasad
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Correspondence to S. Prasad.

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Rajaneesh Kumar Gupta and S. Prasad dedicated the manuscript to Professor M. S. Kanungo, father of aging research in India, who died in July 2011.

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Gupta, R.K., Prasad, S. Differential Regulation of GLT-1/EAAT2 Gene Expression by NF-κB and N-myc in Male Mouse Brain During Postnatal Development. Neurochem Res 39, 150–160 (2014). https://doi.org/10.1007/s11064-013-1200-3

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  • DOI: https://doi.org/10.1007/s11064-013-1200-3

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