Kostrzewa R M, Hardin J C, Jacobowitz D M
Department of Pharmacology, East Tennessee State University, Quillen-Dishner College of Medicine, Johnson City 37614.
Brain Res. 1988 Mar 1;442(2):321-8. doi: 10.1016/0006-8993(88)91518-1.
Although insult of the developing noradrenergic neuronal system in the brain has been associated with redistribution of noradrenergic fiber input to various target brain regions, few studies have investigated the effects of such insults on locus coeruleus cell survival. In the present study the dorsal noradrenergic bundle was transected by means of a midbrain knife cut in rats 3 days after birth, and the effects of this lesion were determined approximately 8-10 weeks later. By means of an immunofluorescent histochemical procedure, it was shown that tyrosine hydroxylase-containing fibers and dopamine beta-hydroxylase-containing fibers were markedly reduced in number in the neocortex and hippocampus--regions anterograde to the site of axonal transection. It was further demonstrated that the number of fluorescent fibers coursing through the dorsal bundle was similarly reduced. Sprouting of noradrenergic fibers in the brainstem and cerebellum accompanied the above alterations. When locus coeruleus cell number was determined by counting Cresyl violet-stained nucleoli in serial sections it was found that dorsal bundle transection produced a loss of 17% of the cells of the coeruleus. By dividing the counts for each nucleus into fifths, it was additionally found that approximately 20-25% of those cells comprising the midportion of the nucleus, along a rostrocaudal axis, were the ones destroyed by axonal transection. These findings indicate that a neonatal lesion of the dorsal bundle produces a loss of cells in the midportion of the nucleus locus coeruleus, and that this effect is associated with noradrenergic neuronal hyperinnervation of the brainstem and cerebellum.
虽然发育中的脑内去甲肾上腺素能神经元系统受到损伤与去甲肾上腺素能纤维输入到各个脑靶区的重新分布有关，但很少有研究调查这种损伤对蓝斑核细胞存活的影响。在本研究中，出生3天后的大鼠通过中脑刀切断术横断背侧去甲肾上腺素能束，并在大约8 - 10周后确定该损伤的影响。通过免疫荧光组织化学方法显示，在新皮层和海马体（轴突横断部位前方的区域）中，含酪氨酸羟化酶的纤维和含多巴胺β-羟化酶的纤维数量明显减少。进一步证明，穿过背侧束的荧光纤维数量也同样减少。脑干和小脑中去甲肾上腺素能纤维的发芽伴随着上述改变。当通过对连续切片中苏木精染色的核仁进行计数来确定蓝斑核细胞数量时，发现背侧束横断导致蓝斑核17%的细胞丢失。通过将每个核的计数分成五等份，还发现沿着前后轴，构成核中部的那些细胞中约20 - 25%被轴突横断破坏。这些发现表明，背侧束的新生期损伤导致蓝斑核中部细胞丢失，并且这种效应与脑干和小脑的去甲肾上腺素能神经元过度支配有关。
