The expression of TRIAD1 and DISC1 after traumatic brain injury and its influence on NSCs

Rui Jiang,Junzhong Yao,Hui Zhu,Wei Shi,Yong Dai,Yazhou Liu,Pei Pei Gong,Qianqian Liu

doi:10.1186/s13287-018-1024-9

Abstract

BackgroundAfter cerebral injury, the proliferation and differentiation of neural stem cells are important for neural regeneration.MethodsWe used the SD rat to establish the traumatic brain injury model. Then, we verified molecular expression, interaction through Western blot, immunoprecipitation (IP), immunofluorescence, and other methods. All data were analyzed with Stata 8.0 statistical software.ResultsWe showed for the first time that the interaction of TRIAD1 and DISC1 plays an important role in neural stem cell proliferation and differentiation after traumatic brain injury. In a rat model of traumatic brain injury, we found that the expression of TRIAD1 increased progressively, reached a peak at 3 to 5 days, and then decreased gradually. While the expression level of DISC1 was correlated with TRIAD1, its expression level at 3 days was significantly lower than at other time points. Immunofluorescence on frozen brain sections showed that TRIAD1 and DISC1 are co-localized in neural stem cells. Immunoprecipitation data suggested that TRIAD1 may interact with DISC1. We transfected 293T tool cells with plasmids containing truncated fragments of TRIAD1 and DISC1 and used additional IPs to reveal that these two proteins interact via specific fragments. Finally, we found that overexpressing TRIAD1 and DISC1 in primary neural stem cells, via lentiviral transfection, significantly affected the proliferation and differentiation of those neural stem cells.ConclusionsTaken together, these data show that the expression of TRIAD1 and DISC1 change after traumatic brain injury and that their interaction may affect the proliferation and differentiation of neural stem cells. Our research may provide a sufficient experimental basis for finding molecular targets for neural stem cell proliferation and differentiation.Trial registrationWe did not report the results of a health care intervention on human participants.

Highlights

IntroductionThe proliferation and differentiation of neural stem cells are important for neural regeneration
After cerebral injury, the proliferation and differentiation of neural stem cells are important for neural regeneration
DISC1 expression gradually decreased starting at 12 h following Traumatic brain injury (TBI), with its lowest point at day 3 compared with the control group (Fig. 1a)

Summary

Introduction

The proliferation and differentiation of neural stem cells are important for neural regeneration. The pathophysiology of TBI includes primary injury caused by direct damage through the initial source of trauma and secondary injury caused by biochemical responsive cascades after subdural hemorrhage and cerebral contusion, such as hypoxia, It should be noted that the use of NSCs to treat brain damage still faces many difficulties. Jiang et al Stem Cell Research & Therapy (2018) 9:297 of NSCs, as well as their differentiation into neurons or oligodendrocytes [8], is among the other major problems restricting the success of this treatment option in TBI. DISC1-encoded scaffold proteins can regulate neurogenesis, as well as the proliferation, migration, and differentiation of NSCs [10]. Ju Young Kim and colleagues show that DISC1 can bind the Girdin protein and affect the proliferation of NSCs by regulating downstream signaling pathways [11]. DISC1 itself is a transcription factor, which may be involved in the transcriptional regulation of NSC-related molecules, thereby affecting the differentiation of NSCs [13]

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Discussion

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