The effect of Hes1 upregulation on neurogenesis after traumatic brain injury

Abstract

Objective To investigate the effect of Hes1 upregulation by using an adonoviral vector containing mouse Hes1 gene in adult hippocampal neurogenesis following traumatic brain injury (TBI), a Morris water maze (MWM) test was employed to investigate the spatial learning and memory capacity of adult mice following injury. Methods One hundred and sixty mice were randomly allocated into four groups: sham-PBS group, sham-PBS-TBI group, Ad5-enhanced green fluorescent protein (EGFP)-TBI group, Ad5-Hes1-TBI group. The TBI model mouse was subjected to lateral fluid percussion injury of (202±2) kPa using a pre-calibrated fluid percussion injury device. Then, Ad5-mRNA and PBS were stereotaetic injected into the hippocampus of the adult C57BL/6 mice and their expressions in the hippocampus were detected. Western blotting and real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) methods were employed to detect the expression level of Hes1 on day 3 following TBI. We performed BrdU or DCX immunofluorescence staining on day 3 or 7 post TBI, to investigate the effect of Hes1 upregulation in adult hippocampal neurogenesis following TBI. Results FQ-PCR and Western blotting analysis suggested that Hes1 was up-regulated in overexpression group at mRNA (1.87±0.13 vs. 0.97±0.13, P=0.025) on day 3 post TBI and protein level; Immunofluorescence staining showed that a significant decrease in the total number of BrdU (+ ) and DCX (+ ) cells from the animals with Ad5-mHes1 treated on day 3 or 7 post injury. Morris water maze (MWM) test confirmed that Hes1 overexpression did not lead to a statistically significant change in EL and the target quadrant (P=0.062). Conclusion These results strongly suggested that increased expression of Hes1 may inhibit adult neurogenesis in DG of hippocampus after TBI and did not lead to a statistically significant change in the spatial learning and memory capacity of adult mice following injury. Key words: Hes1; Adult neurogenesis; Traumatic brain injury; Morris water maze