title: Differential regulation of GLT-1/EAAT2 gene expression by NF-κB and N-myc in male mouse brain during postnatal development.
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.
authors.affiliation: Molecular Biology and Biochemistry Lab., Centre of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India.
authors.forename: Rajaneesh Kumar
authors.initials: RK
authors.lastname: Gupta
authors.forename: S
authors.initials: S
authors.lastname: Prasad
mesh_terms: D000818:Animals; D002525:Cerebellar Cortex / Q000254:growth & development* / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc