Hamers F P, Plantinga L C, Verhaagen J, Neijt J P, Gispen W H
Rudolf Magnus Institute, Department of Medical Pharmacology, Utrecht University, The Netherlands.
J Neurosci Res. 1996 Apr 15;44(2):142-8. doi: 10.1002/(SICI)1097-4547(19960415)44:2<142::AID-JNR6>3.0.CO;2-D.
Expression of the growth-associated protein B50 (GAP-43) mRNA in dorsal root ganglia (DRG) of rats was studied by in situ hybridization. In response to treatment with the neurotoxic agent cisplatin, B50 mRNA expression was significantly enhanced following a cumulative cisplatin dose of 14 mg/kg. In the untreated age-matched control animals, only half of the ganglion cells exhibited expression of B50 mRNA (mean hybridization signal, 10 times background), whereas at a cumulative cisplatin dose of 14 mg cisplatin every neuron exhibited well above background expression (mean hybridization signal, 34 times background). Cotreatment with a neuroprotective ACTH4-9 analog known to prevent cisplatin neuropathy in rats did not affect the overall expression of B50 mRNA. However, in the subpopulation of large sensory neurons, B50 mRNA content was significantly higher in the group cotreated with the ACTH4-9 analog as compared with the saline-cotreated group after 14 mg/kg of cisplatin. We conclude that in analogy with the well-known upregulation of B50 mRNA following mechanical nerve lesions, treatment with the neurotoxic drug cisplatin also leads to an increase in B50 mRNA expression. This observation lends strength to the hypothesis that in neuropathies an imbalance between regenerative and degenerative mechanisms exists. The ability of the larger sensory neurons to retain an increased B50 mRNA expression better after cotreatment with the peptide than without may be related to stimulation of regenerative processes by this ACTH4-9 analog.
采用原位杂交技术研究了大鼠背根神经节（DRG）中生长相关蛋白B50（GAP - 43）mRNA的表达。给予神经毒性药物顺铂治疗后，当顺铂累积剂量达到14mg/kg时，B50 mRNA表达显著增强。在未经治疗的年龄匹配对照动物中，只有一半的神经节细胞表现出B50 mRNA表达（平均杂交信号，为背景的10倍），而当顺铂累积剂量为14mg时，每个神经元均表现出远高于背景的表达（平均杂交信号，为背景的34倍）。与一种已知可预防大鼠顺铂神经病变的神经保护ACTH4 - 9类似物联合治疗，并不影响B50 mRNA的整体表达。然而，在大感觉神经元亚群中，给予14mg/kg顺铂后，与生理盐水联合治疗组相比，ACTH4 - 9类似物联合治疗组的B50 mRNA含量显著更高。我们得出结论，与机械性神经损伤后B50 mRNA的上调情况类似，神经毒性药物顺铂治疗也会导致B50 mRNA表达增加。这一观察结果支持了神经病变中再生和退变机制之间存在失衡的假说。与未联合治疗相比，较大感觉神经元在与该肽联合治疗后能更好地维持增加的B50 mRNA表达，这可能与该ACTH4 - 9类似物对再生过程的刺激有关。
