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

作者：Gupta Rajaneesh Kumar; Prasad S^*

来源：Neurochemical Research, 2014, 39(1): 150-160.

DOI：10.1007/s11064-013-1200-3

• Glia
• Glutamate
• GLT-1
• EAAT2
• NF-kappa B
• N-myc
• Postnatal development
• Aging

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-kappa B 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-kappa B 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-kappa B 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-kappa B 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.

• 出版日期2014-1