Age-Dependent Alterations in the Interactions of NF-kappa B and N-myc with GLT-1/EAAT2 Promoter in the Pericontusional Cortex of Mice Subjected to Traumatic Brain Injury

摘要

Traumatic brain injury (TBI) is one of the major risk factors of dementia, aging, and cognitive impairments, etc. We have previously reported that expression of the astrocytic glutamate transporter GLT-1/EAAT2 is downregulated in the pericontusional cortex of adult and old mice in post-TBI time-dependent manner, and the process of decline starts before in old than in adult TBI mice. However, relationship between age- and TBI-dependent alterations in GLT-1/EAAT2 expression and interactions of transcription factors NF-kappa B and N-myc with their cognate GLT-1/EAAT2 promoter sequences, an important step of its transcriptional control, is not known. To understand this, we developed TBI mouse model by modified chronic head injury (CHI) method, analyzed expression of GFAP, TNF-alpha, and AQP4 by RT-PCR for its validation, and analyzed interactions of NF-kappa B and N-myc with GLT-1/EAAT2 promoter sequences by electrophoretic mobility shift assay (EMSA). Our EMSA data revealed that interactions of NF-kappa B and N-myc with GLT-1/EAAT2 promoter sequences was significantly elevated in the ipsi-lateral cortex of both adult and old TBI mice in post-TBI time-dependent manner; however, these interactions started immediately in the old compared to that in adult TBI mice, which could be attributed to our previously reported age- and post-TBI time-dependent differential expression of GLT-1/EAAT2 in the pericontusional cortex.