Background By unbiased stereological methods, we have observed preferential dorsal root ganglion （DRG） B-cell loss in rodents after nerve injury, and caspase-3 activation and cell loss were related to the present of...Background By unbiased stereological methods, we have observed preferential dorsal root ganglion （DRG） B-cell loss in rodents after nerve injury, and caspase-3 activation and cell loss were related to the present of p75 receptor （p75^NTR）. We hypothesized that DRG B-cells express higher levels of pro-apoptotic proteins as compared to A-cells and the expressions of pro-apoptotic proteins can be reduced by depletion of p75^NTR. This study aimed to identify the p75NTR involved apoptotic pathway in DRG neurons after nerve injury. Methods The p75NTR knockout mice （p75-/-） and wildtype Balb/C mice （p75＋/＋） were used in this study. The expressions of pro-apoptotic proteins, c-Jun-N-terminal kinase （JNK）, c-jun and p38 in DRG were evaluated with immunohistochemistry 2 and 7 days following unilateral sciatic nerve transection. In addition, extra-cellular related kinase （ERK）, a transducer of survival signals, was also tested with immunohistochemistry and Western blotting methods in these animal models. Results Phosphorylated JNK （P-JNK） and phosphorylated p38 （P-p38） were mainly located in small B-cells, whereas phosphorylated c-jun （P-c-jun） was located in both A- and B-cells. Phosphorylated ERK （P-ERK） was located in both B-cells and satellite cells. Axotomy dramatically increased the expressions of P-JNK and P-c-jun （paired t-test）, with no influence on the expressions of P-p38 and P-ERK. Furthermore, the increase of P-JNK in p75＋/＋ mice 2 days after nerve axotomy was approximately 2.2-folds of that in p75-/- mice （P=-0.001, unpaired t-test）. Conclusion p75NTR-dependent JNK-caspase-3 pathway is involved in DRG B-cell loss after nerve injury and JNK is not the unique upstream of c-jun activation.展开更多
文摘Background By unbiased stereological methods, we have observed preferential dorsal root ganglion （DRG） B-cell loss in rodents after nerve injury, and caspase-3 activation and cell loss were related to the present of p75 receptor （p75^NTR）. We hypothesized that DRG B-cells express higher levels of pro-apoptotic proteins as compared to A-cells and the expressions of pro-apoptotic proteins can be reduced by depletion of p75^NTR. This study aimed to identify the p75NTR involved apoptotic pathway in DRG neurons after nerve injury. Methods The p75NTR knockout mice （p75-/-） and wildtype Balb/C mice （p75＋/＋） were used in this study. The expressions of pro-apoptotic proteins, c-Jun-N-terminal kinase （JNK）, c-jun and p38 in DRG were evaluated with immunohistochemistry 2 and 7 days following unilateral sciatic nerve transection. In addition, extra-cellular related kinase （ERK）, a transducer of survival signals, was also tested with immunohistochemistry and Western blotting methods in these animal models. Results Phosphorylated JNK （P-JNK） and phosphorylated p38 （P-p38） were mainly located in small B-cells, whereas phosphorylated c-jun （P-c-jun） was located in both A- and B-cells. Phosphorylated ERK （P-ERK） was located in both B-cells and satellite cells. Axotomy dramatically increased the expressions of P-JNK and P-c-jun （paired t-test）, with no influence on the expressions of P-p38 and P-ERK. Furthermore, the increase of P-JNK in p75＋/＋ mice 2 days after nerve axotomy was approximately 2.2-folds of that in p75-/- mice （P=-0.001, unpaired t-test）. Conclusion p75NTR-dependent JNK-caspase-3 pathway is involved in DRG B-cell loss after nerve injury and JNK is not the unique upstream of c-jun activation.
