ACUTE ACTION OF DSP-4 ON CENTRAL NOREPINEPHRINE AXONS - BIOCHEMICAL AND IMMUNOHISTOCHEMICAL EVIDENCE FOR DIFFERENTIAL-EFFECTS
ACUTE ACTION OF DSP-4 ON CENTRAL NOREPINEPHRINE AXONS - BIOCHEMICAL AND IMMUNOHISTOCHEMICAL EVIDENCE FOR DIFFERENTIAL-EFFECTS
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DOI：
10.1177/37.9.2768812
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发表时间：
1989-09-01
影响因子：
3.2
通讯作者：
GEFFARD, M
中科院分区：
文献类型：
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作者：
GRZANNA, R;BERGER, U;GEFFARD, M
以前的长期影响的去甲肾上腺素能神经毒素DSP-4的免疫组织化学研究已经证明了显着的选择性的蓝斑（LC）的去甲肾上腺素（NE）轴突的脆弱性。起源于非LC NE神经元的NE轴突似乎在很大程度上对DSP-4的神经毒性作用具有抗性。我们进行了这项研究，以评估DSP-4对NE轴突在四个不同的大脑区域：大脑皮层，小脑，腹前脑，下丘脑的急性影响。在DSP-4给药后6和24小时以及14天，通过高效液相色谱法（HPLC）测定NE水平。在药物治疗后6和24小时，使用NE的特异性抗血清在脑切片中观察这些脑区域中的NE轴突。HPLC分析显示，大脑皮层和小脑中的NE水平显著降低，但腹侧前脑和下丘脑中的NE水平仅轻微降低。NE免疫组织化学显示DSP-4对NE轴突染色的急性效应的显著差异：与腹侧前脑和下丘脑中几乎不变的染色模式相反，皮质和小脑中的染色几乎完全丧失。本研究表明NE免疫组织化学是评估DSP-4对不同脑区NE轴突的急性作用的有价值的工具。结果提供了第一个直接证据，即NE轴突不均匀地作用于DSP-4，并表明DSP-4的急性作用仅限于LC轴突。
Previous immunohistochemical studies of the long-term effects of the noradrenergic neurotoxin DSP-4 have demonstrated a remarkably selective vulnerability of norepinephrine (NE) axons of the locus coeruleus (LC). NE axons originating in non-LC NE neurons appear to be largely resistant to the neurotoxic action of DSP-4. We conducted this study to evaluate the acute effects of DSP-4 on NE axons in four different brain regions: cerebral cortex, cerebellum, ventral forebrain, and hypothalamus. NE levels were determined by high-performance liquid chrommatography (HPLC) 6 and 24 hr and 14 days after DSP-4 administration. NE axons in these brain regions were visualized in brain sections at 6 and 24 hr after drug treatment, using a specific antiserum to NE. HPLC assays revealed profound reductions of NE levels in cerebral cortex and cerebellum, but only minor decreases in ventral forebrain and hypothalamus. NE immunohistochemistry showed dramatic difference in the acute effects of DSP-4 on NE axon staining: nearly complete loss of staining in cortex and cerebellum, in contrast to an almost unchanged staining pattern in ventral forebrain and hypothalamus. This study demonstrates the NE immunohistochemistry is a valuable tool to assess the acute effects of DSP-4 on NE axons in different brain regions. The results provide the first direct evidence that NE axons are not uniformly acted on by DSP-4 and suggest that the acute effects of DSP-4 are restricted to LC axons.