Background: After cerebral injury, the proliferation and differentiation of neural stem cells are important for neural regeneration.
Methods: We 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.
Results: We 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.
Conclusions: Taken 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 registration: We did not report the results of a health care intervention on human participants.
Keywords: DISC1; Differentiation; NSCs; Proliferation; TRIAD1; Traumatic brain injury.