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. 2014 Jan;39(1):150-60.
doi: 10.1007/s11064-013-1200-3. Epub 2013 Nov 26.

Differential regulation of GLT-1/EAAT2 gene expression by NF-κB and N-myc in male mouse brain during postnatal development

Rajaneesh Kumar Gupta  1 , S Prasad
Affiliations

Differential regulation of GLT-1/EAAT2 gene expression by NF-κB and N-myc in male mouse brain during postnatal development

Rajaneesh Kumar Gupta et al. Neurochem Res. 2014 Jan.

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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