Differential effect of traumatic brain injury on the nuclear factor of activated T Cells C3 and C4 isoforms in the rat hippocampus

Abstract

The interaction between the phosphatase calcineurin and transcription factor nuclear factor of activated T cells (NFAT) plays an important role numerous signaling and the regulatory events. Although NFAT is mostly known for its transcription function in the immune system, NFAT also has essential functions even in the central nervous system (CNS). The effects of traumatic brain injury (TBI) on NFAT are currently unknown. To determine if there is an alteration in NFAT after TBI, we examined NFATc3 and c4 levels at 6h, 1 day, 1 week, 2 weeks and 4 weeks post injury. Rats were anesthetized and surgically prepared for controlled cortical impact (CCI) injury or sham surgery. Semi-quantitative measurements of NFATc3 and c4 in the hippocampal homogenates from injured and sham rats sacrificed at the appropriate time after injury were assessed using Western blot analysis. After TBI insult, in the hippocampus ipsilateral to the injury, NFATc3 expression levels were decreased both in the cytoplasmic and nuclear fractions. However, NFATc4 expression levels were increased in the cytoplasmic fraction but decreased in the nuclear fraction. Double labeling (with NeuN and GFAP) immunohistochemistry revealed that NFATc3 was expressed in subset of astrocytes and NFATc4 was expressed primarily in neurons. These differential responses in NFATc3 and c4 expression after TBI insult may indicate long-term changes in hippocampal excitability and may contribute to behavioral deficits. Further study is warranted to illustrate the role of NFATc3 and c4 in the setting of TBI.