Fritschy J M, Geffard M, Grzanna R
Johns Hopkins University School of Medicine, Department of Neuroscience, Baltimore, Maryland 21205.
J Chem Neuroanat. 1990 Jul-Aug;3(4):309-21.
The response of noradrenaline (NA) axons to the effects of systemic injections of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was studied in the rat brain. Antibodies to NA and to dopamine-beta-hydroxylase (DBH) were employed to assess by immunohistochemistry the effects of DSP-4 on NA axons between 6 h and 2 weeks after drug administration. The changes in NA and DBH staining after DSP-4 treatment were restricted to brain regions innervated by the locus coeruleus. In these areas, DSP-4 induced profound loss of both NA and DBH from NA axons, but with a distinctly different time-course. While NA disappeared within hours after drug treatment, DBH staining of NA axons remained unchanged during the first 4 days after DSP-4 treatment. Thereafter, there was an abrupt loss of DBH staining which coincided with the appearance of numerous brightly stained, thick and swollen NA axons. The distribution of these fibres suggests that they represent the distal ends of preterminal NA axons. Two weeks after drug treatment, NA axons could no longer be visualized by either NA or DBH immunohistochemistry in regions affected by DSP-4. During this 2-week time-period, the staining of cell bodies in the locus coeruleus and of ascending NA axons in the dorsal bundle was unaffected. The results suggest two phases in the response of NA axons to DSP-4: an acute phase, marked by loss of transmitter, and a neurodegenerative phase, characterized by loss of DBH and structural disintegration of NA axons.
在大鼠脑中研究了去甲肾上腺素（NA）轴突对全身注射N-（2-氯乙基）-N-乙基-2-溴苄胺（DSP-4）作用的反应。使用抗NA和抗多巴胺-β-羟化酶（DBH）抗体，通过免疫组织化学评估给药后6小时至2周内DSP-4对NA轴突的影响。DSP-4处理后NA和DBH染色的变化仅限于蓝斑支配的脑区。在这些区域，DSP-4导致NA轴突中NA和DBH均大量丧失，但时间进程明显不同。药物处理后数小时内NA消失，而DSP-4处理后的前4天内NA轴突的DBH染色保持不变。此后，DBH染色突然丧失，与此同时出现大量染色明亮、粗大且肿胀的NA轴突。这些纤维的分布表明它们代表终末前NA轴突的远端。药物处理2周后，在受DSP-4影响的区域，通过NA或DBH免疫组织化学均无法再观察到NA轴突。在这2周的时间段内，蓝斑中的细胞体染色以及背束中上行NA轴突的染色均未受影响。结果表明NA轴突对DSP-4的反应有两个阶段：急性期，以递质丧失为特征；神经退行性阶段，以DBH丧失和NA轴突结构解体为特征。
