Correlation between the proliferation ability of neural stem cells in hippocampus and PTEN/Akt/mTOR signaling pathway post traumatic brain injury in rats

Abstract

Objective To study the correlation between the proliferation ability of neural stem cells (NSCs) in hippocampus and the phosphatase and tensin homolog deleted on chromosome 10/protein kinase B/mammalian target of rapamycin (PTEN/Akt/mTOR) signaling pathway after traumatic brain injury (TBI). Methods A total of 18 rats were randomly divided into sham group (6 rats) and TBI group (12 rats). The TBI model was constructed by the controlled cortical injury (CCI) device. Another 24 rats were randomly divided into TBI+ saline group (12 rats) and TBI+ bisperoxovanadium (BPV) group (12 rats). The rats in TBI+ saline group (12 rats) and TBI+ BPV group were intraperitoneally injected with BPV (total amount was 20 μg/100 g, 4 times, once/4 h) or same amount of saline at 24 h before the construction of TBI. The brain was isolated from rats of at 7 days post TBI, the proliferation ability of NSCs (BrdU/Sox2 double positive cells) and expression of PTEN in hippocampus were measured by immunofluorescence, and Western blot was performed to measure the expression of PTEN and PTEN/Akt/mTOR signaling pathway molecules. Results Compared with the sham group, the number of BrdU/Sox2 double positive NSCs was significantly increased (sham: 30.3±2.3, TBI: 113.4±3.9, P<0.01), the expression of PTEN was significantly decreased (sham: 2.13±0.04, TBI: 1.03±0.07, P<0.01), and the expression of PTEN was negatively correlated with the number of BrdU/Sox2 double positive NSCs in TBI group (r=-0.948, P<0.01). Compared with the TBI+ saline group, the number of BrdU/Sox2 double positive NSCs was significantly increased (TBI+ saline: 117.5±6.6, TBI+ BPV: 135.8±7.4, P<0.01), the expression of PTEN was significantly decreased (TBI+ saline: 1.32±0.08, TBI+ BPV: 0.64±0.03, P<0.01), and the phosphorylation ratio of Akt and mTOR was significantly elevated in TBI+ BPV group (ratio of p-mTOR/mTOR, TBI+ saline: 0.93±0.12, TBI+ BPV: 2.15±0.16, P<0.01; ratio of p-Akt/Akt, TBI+ saline: 1.08±0.11, TBI+ BPV: 1.95±0.19, P<0.01). Conclusion The proliferation ability of NSCs in hippocampus is elevated after TBI and enhanced by the inhibition of PTEN, which might be correlated with the PTEN/Akt/mTOR signaling pathway. Key words: Craniocerebral trauma; Neural stem cells; Hippocampus; Rats; Phosphatase and tensin homolog deleted onchromosome 10