RELATIVE SURVIVAL OF STRIATAL PROJECTION NEURONS AND INTERNEURONS AFTER INTRASTRIATAL INJECTION OF QUINOLINIC ACID IN RATS
RELATIVE SURVIVAL OF STRIATAL PROJECTION NEURONS AND INTERNEURONS AFTER INTRASTRIATAL INJECTION OF QUINOLINIC ACID IN RATS
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DOI：
10.1006/exnr.1994.1145
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发表时间：
1994-09-01
影响因子：
5.3
通讯作者：
REINER, A
中科院分区：
文献类型：
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作者：
FIGUEREDOCARDENAS, G;ANDERSON, KD;REINER, A
NMDA型谷氨酸受体介导的兴奋毒性过程可能参与了亨廷顿病(HD)纹状体神经元的死亡。为了探索这种可能性，我们向成年大鼠的纹状体注射了一种NMDA受体特异性的兴奋性毒素-喹啉酸(QA)，并在损伤后2-4个月观察了不同类型的纹状体投射神经元和中间神经元以及不同纹状体投射区域的纹状体传出纤维的相对存活模式。用神经递质免疫组织化学标记或纹状体靶区逆行标记特定类型纹状体神经元的核膜，用神经递质免疫组织化学标记纹状体传出神经丛。确定了每种神经元类型的核膜存活模式，作为距离注射部位中心的距离的函数，并比较了每种类型的相对存活率。对于靶区的纤维，使用计算机辅助图像分析来确定每个投射靶点的纤维损失程度。在对黄体周围易损性的研究中，我们发现生长抑素-神经肽Y(SS/NPY)中间神经元对QA最敏感，胆碱能神经元对QA不敏感。所有类型的投射神经元(纹状体、纹状体和纹状体-内侧)的核膜比SS/NPY中间神经元更脆弱，而比胆碱能中间神经元更脆弱。在投射神经元周围，有证据表明有不同的脆弱性，其中纹状体黑质神经元似乎是最脆弱的。对纹状体靶区内免疫标记的纹状体纤维的检查表明，纹状体内侧丘脑纤维比纹状体苍白质或纹状体黑质纤维更能在纹状体QA中存活。在本研究中观察到的投射神经元和/或其传出神经丛的易损性和在本研究中观察到的胆碱能中间神经元的抗毁性与在HD中观察到的相似。然而，SS/NPY中间神经元对QA的脆弱性与它们在HD中的抗毁性形成鲜明对比。结果表明，虽然兴奋性毒素假说在KD时纹状体神经元死亡是成立的，但成年大鼠纹状体内注射QA并不能严格地模拟HD的结局。这表明，要么成年大鼠不是完全适合模拟HD的对象，要么HD兴奋毒性过程不涉及自由循环的兴奋性毒素，如QA。(C)1994年学术出版社。
An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington's disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in KD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA. (C) 1994 Academic Press, Inc.