Gorio A, Di Giulio A M, Germani E, Bendotti C, Bertelli A, Mantegazza P
Department of Medical Pharmacology, Faculty of Medicine, University of Milano, Italy.
J Neurosci Res. 1993 Mar 1;34(4):462-71. doi: 10.1002/jnr.490340411.
Lesion of the serotoninergic system in neonate rats is an ideal model for assessing the activity of chemical substances capable of affecting neuronal plasticity and regeneration (Jonsson et al., Dev Brain Res 16: 171-180, 1984). Treatment of newborn rats within 6 hr from birth with the selective neurotoxin 5,7-dihydroxytryptamine causes degeneration of the most distal serotoninergic axons. In our experimental conditions we have observed that after such neurotoxic treatment there is spinal cord denervation, which is particularly remarkable in the lumbar segment. This degenerative event is followed by gradual regeneration of the lesioned axons, with good reinnervation of the entire cord within 8 weeks. The degeneration-regeneration process is correlated with a transient hyperinnervation of the pons-medulla and hypothalamus by the short collaterals (pruning effect), as evidenced by increased serotonin content. Perinatal morphine exposure markedly impairs serotonin regeneration in the spinal cord. In addition, opiate treated rats are more susceptible to lesions, as shown by the neurotoxin induced denervation of the cortex, pons-medulla, and hypothalamus, which does not occur in lesioned controls. Therefore, our observations suggest that perinatal exposure to morphine affects the plasticity and regeneration of the developing serotoninergic system by increasing its susceptibility to neurotoxic lesions and reducing its regenerative capacity.
新生大鼠血清素能系统损伤是评估能够影响神经元可塑性和再生的化学物质活性的理想模型（Jonsson等人，《发育脑研究》16: 171 - 180，1984年）。在出生后6小时内用选择性神经毒素5,7 - 二羟基色胺处理新生大鼠，会导致最远端的血清素能轴突发生退化。在我们的实验条件下，我们观察到在这种神经毒性处理后会出现脊髓去神经支配，这在腰段尤为明显。这种退化事件之后是受损轴突的逐渐再生，在8周内整个脊髓能实现良好的再支配。退化 - 再生过程与短侧支对脑桥 - 延髓和下丘脑的短暂过度支配（修剪效应）相关，血清素含量增加证明了这一点。围产期吗啡暴露显著损害脊髓中的血清素再生。此外，如神经毒素诱导的皮质、脑桥 - 延髓和下丘脑去神经支配所示，经阿片类药物处理的大鼠更容易受到损伤，而在受损对照组中则不会出现这种情况。因此，我们的观察结果表明，围产期接触吗啡会通过增加发育中的血清素能系统对神经毒性损伤的易感性并降低其再生能力，从而影响其可塑性和再生。
