gp120, a human immunodeficiency virus-1 coat protein, augments excitotoxic hippocampal injury in perinatal rats
gp120, a human immunodeficiency virus-1 coat protein, augments excitotoxic hippocampal injury in perinatal rats
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DOI：
10.1016/s0306-4522(96)00373-9
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发表时间：
1997-01-01
期刊：
影响因子：
3.3
通讯作者：
Silverstein, FS
中科院分区：
文献类型：
--
作者：
Barks, JDE;Liu, XH;Silverstein, FS
最近的数据表明，gp 120，人类免疫缺陷病毒-1（HIV-I）煤糖蛋白，是由HIV感染的细胞分泌，是神经毒性，这种毒性介导的，至少部分，通过激活N-甲基-D-天冬氨酸型兴奋性氨基酸受体。为了测试这一假设在体内，我们研究了神经毒性的gp 120注射intraperitoneal campally，单独或共同注射的选择性兴奋性，氨基酸激动剂N-甲基-D-天冬氨酸，在7天大的大鼠。5天后，使用三种结果指标评估损伤海马的损伤严重程度：组织病理学、海马萎缩（来自区域横截面积测量）和[H-3]谷氨酸受体结合丧失（基于体外放射自显影测定）。为了证实所有观察到的效应均归因于gp 120生物活性，每组实验包括接受等量热处理gp 120的对照组。Gp 120（200 ng）引起紧邻注射轨迹的最小局灶性锥体细胞损失;没有海马萎缩或[H-3]谷氨酸结合损失。共注射50 ng gp 120和N-甲基-D-天冬氨酸（5 nmol，阈兴奋毒性剂量）增加海马损伤程度;海马萎缩在接受5 nmol N-甲基-D-天冬氨酸与50 ng gp 120联合注射的动物中比在接受单独的N-甲基-D-天冬氨酸（5 nmol）或5 nmol N-甲基-D-天冬氨酸+50 ng热的动物中更大。处理gp 120（平均值+/-S.E.M，注射海马体积相对于对侧的减少百分比：N-甲基-D-天冬氨酸，-19+/-3; N-甲基-D-天冬氨酸+gp 120，-26.8+/-2.1; N-甲基-D-天冬氨酸+热处理gp 120，-14.0+/-2.2; P
Recent data suggest that gp120, a human immunodeficiency virus-1 (HIV-I) coal glycoprotein that is secreted by HIV-infected cells, is neurotoxic, and that this toxicity is mediated, at least in part, by activation of N-methyl-D-aspartate-type excitatory amino acid receptors. To lest this hypothesis in vivo, we examined the neurotoxicity of gp120 injected intrahippocampally, alone or co-injected with the selective excitatory, amino acid agonist N-methyl-D-aspartate, in seven-day-old rats. Severity of injury in the lesioned hippocampus was assessed five days later, using three outcome measures: histopathology, hippocampal atrophy (derived from regional cross-sectional area measurements) and loss of [H-3]glutamate receptor binding (based on in vitro autoradiography assays). To confirm that ally observed effects were attributable to gp120 bioactivity, each group of experiments included controls that received equal amounts of heat-treated gp120.Gp120 (200 ng) elicited minimal focal pyramidal cell loss immediately adjacent to the injection track; there was no hippocampal atrophy or loss of [H-3]glutamate binding. Co-injection of 50 ng gp120 with N-methyl-D-aspartate (5 nmol, threshold excitotoxic dose) increased the severity of hippocampal injury; hippocampal atrophy was greater in animals that received injections of 5 nmol N-methyl-D-aspartate in combination with 50 ng gp120 than in those that received either N-methyl-D-aspartate alone (5 nmol) or 5 nmol N-methyl-D-aspartate+50 ng heat-treated gp120 (mean+/-S.E.M, percentage reduction in injected hippocampal volume vs contralateral: N-methyl-D-aspartate, -19+/-3; N-methyl-D-aspartate+gp120, -26.8+/-2.1; N-methyl-D-aspartate+heat-treated gp120, -14.0+/-2.2; P