Sun Z, Chen Q, Reiner A
Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Exp Neurol. 2003 Dec;184(2):1034-42. doi: 10.1016/j.expneurol.2003.08.016.
While the excitotoxic vulnerability of striatal neurons is known to be greater in juvenile than adult animals, it is uncertain if striatal neuron types decline differentially in their vulnerability with age. To examine this issue, we unilaterally injected quinolinic acid (QA), an N-methyl-d-aspartate (NMDA) receptor agonist, into the striatum of juvenile and adult rats, and used in situ hybridization histochemistry with oligonucleotide probes for preproenkephalin and preprotachykinin mRNA to label surviving enkephalinergic (ENK) and substance P-containing (SP) neurons in adjacent sections through the injection center. The results confirmed that the region of severe damage is greater in young than adult animals, but revealed that at the very center of the QA injection, labeled neuron abundance was lower in adult than juvenile striatum. In juvenile rats, the vulnerability of the ENK neurons at all distances from the injection center was the same as that of the SP neurons. By contrast, in adult rats, the ENK neuron survival was greater than the SP neuron survival at all distances beyond the lesion center. The SP neuron survival outside the injection center in the adult rats was similar to that in juvenile rats, while the ENK neuron survival beyond the injection center was better in adult than juvenile rats. These data indicate that there is an age-dependent decrease in the vulnerability of ENK but not SP striatal projection neurons to QA-mediated injury in rats. The results also raise the possibility that, if an excitotoxic process is involved in HD pathogenesis, a differential age-related decline in the sensitivity of striatal projection neuron types to this process may contribute to the more uniform striatal neuron loss in juvenile-onset Huntington's disease (HD) and the more differential loss in adult-onset HD.
虽然已知纹状体神经元的兴奋毒性易损性在幼年动物中比成年动物更大，但尚不确定纹状体神经元类型的易损性是否会随着年龄的增长而出现差异下降。为了研究这个问题，我们将喹啉酸（QA）（一种N-甲基-D-天冬氨酸（NMDA）受体激动剂）单侧注射到幼年和成年大鼠的纹状体中，并使用针对前脑啡肽原和前速激肽原mRNA的寡核苷酸探针进行原位杂交组织化学，以标记通过注射中心的相邻切片中存活的脑啡肽能（ENK）神经元和含P物质（SP）的神经元。结果证实，幼年动物中严重损伤区域比成年动物更大，但显示在QA注射的正中心，成年纹状体中标记神经元的丰度低于幼年纹状体。在幼年大鼠中，距注射中心所有距离处的ENK神经元的易损性与SP神经元相同。相比之下，在成年大鼠中，在病变中心以外的所有距离处，ENK神经元的存活率均高于SP神经元。成年大鼠注射中心以外的SP神经元存活率与幼年大鼠相似，而成年大鼠注射中心以外的ENK神经元存活率比幼年大鼠更好。这些数据表明，大鼠中ENK纹状体投射神经元对QA介导的损伤的易损性存在年龄依赖性下降，而SP纹状体投射神经元则不然。研究结果还提出了一种可能性，即如果兴奋性毒性过程参与亨廷顿舞蹈症（HD）的发病机制，纹状体投射神经元类型对该过程的敏感性与年龄相关的差异下降可能导致幼年型亨廷顿舞蹈症（HD）中纹状体神经元损失更均匀，而成年型HD中损失更具差异性。
