Different apoptotic reactions of dorsal root ganglion A- and B-cells after sciatic nerve axotomy: effect of p75 neurotrophin receptor / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>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 p75(NTR) involved apoptotic pathway in DRG neurons after nerve injury.</p><p><b>METHODS</b>The p75(NTR) 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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>p75(NTR)-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.</p>