Delio D A, Gold B G, Lowndes H E
Department of Pharmacology and Toxicology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855-0789.
Toxicol Appl Pharmacol. 1989 Jun 15;99(2):207-15. doi: 10.1016/0041-008x(89)90003-3.
Motoneurons (MNs) exhibit characteristic electrophysiological alterations following axotomy which are concomitants of perikaryal remodeling induced by the axonal injury. beta,beta'-Iminodipropionitrile (IDPN) neurotoxicity, which produces proximal axonal swellings in the first internodes of motor fibers, was studied as a model of perikaryal electrophysiological properties in axonal pathologies without axonal degeneration. Similarities between parameters of MN excitability (delayed depolarizations, repetitive discharge, and the afterhyperpolarization potential, AHP) known to occur in axotomized MN and those in IDPN neuropathy were examined in type-identified spinal MN of cats during the evolution (7 to 35 days) of proximal axonal swellings. Delayed depolarization potentials were observed frequently in fast MN types throughout the neuropathy but only at 35 days in slow MN types. Similarly, repetitive firing occurred most prominently in fast MNs early in the neuropathy. Concomitantly, AHP duration decreased as early as 7 days in all MN types and was significantly shortened in types FF, FR, and S motoneurons. AHP peak amplitude and current declined continuously from 7 to 35 days of the neuropathy and were significantly (p less than 0.05) decreased at 35 days in types FF and S MNs. These results suggest that not only are fast MN types vulnerable early in IDPN neuropathy, but also that all MN types exhibit electrophysiological changes strikingly similar to those following mechanical axotomy. The possibility is raised that IDPN may initiate electrophysiological changes, analogous to perikaryal remodeling, by mechanism(s) unrelated to axonal degeneration.
运动神经元（MNs）在轴突切断后表现出特征性的电生理改变，这些改变是轴突损伤诱导的胞体重塑的伴随现象。β,β'-亚氨基二丙腈（IDPN）神经毒性可在运动纤维的第一结间段产生近端轴突肿胀，本研究将其作为一种轴突病变但无轴突退变情况下胞体电生理特性的模型。在近端轴突肿胀发展过程（7至35天）中，对猫的已鉴定类型的脊髓运动神经元进行研究，比较轴突切断的运动神经元与IDPN神经病中已知的运动神经元兴奋性参数（延迟去极化、重复放电和超极化后电位，AHP）之间的相似性。在整个神经病过程中，快速运动神经元类型频繁出现延迟去极化电位，而慢速运动神经元类型仅在35天时出现。同样，重复放电在神经病早期最显著地发生在快速运动神经元中。同时，所有运动神经元类型的AHP持续时间早在7天时就开始减少，在FF、FR和S运动神经元类型中显著缩短。从神经病的7天到35天，AHP峰值幅度和电流持续下降，在35天时，FF和S运动神经元类型显著（p<0.05）降低。这些结果表明，不仅快速运动神经元类型在IDPN神经病早期易受影响，而且所有运动神经元类型都表现出与机械性轴突切断后极为相似的电生理变化。这就提出了一种可能性，即IDPN可能通过与轴突退变无关的机制引发类似于胞体重塑的电生理变化。
