LEARNING IMPAIRMENT FOLLOWING INTRACEREBRAL ADMINISTRATION OF THE HIV ENVELOPE PROTEIN GP120 OR A VIP ANTAGONIST
LEARNING IMPAIRMENT FOLLOWING INTRACEREBRAL ADMINISTRATION OF THE HIV ENVELOPE PROTEIN GP120 OR A VIP ANTAGONIST
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DOI：
10.1016/0006-8993(92)90562-n
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发表时间：
1992-01-20
期刊：
影响因子：
2.9
通讯作者：
HILL, JM
中科院分区：
文献类型：
--
作者：
GLOWA, JR;PANLILIO, LV;HILL, JM
人类免疫缺陷病毒（HIV）的外包膜糖蛋白（gp120）已被证明对培养的神经元有毒性。为了进一步研究gp120的神经学作用，我们评估了该蛋白与空间辨别获得的关系。将天然gp120和重组gp120分别注入成年大鼠脑室，并在Morris游泳迷宫中评估其表现。每天给药12 ng后，Gp120治疗延迟了习得。这种损伤的特异性在给予相同量的重组杆状病毒gp160的动物的表现与给予生理盐水的动物没有区别中得到证实。血管活性肠肽（VIP）已被证明可以阻断gp120诱导的神经毒性，VIP受体拮抗剂已显示出对培养神经元的毒性。我们在这里表明，这种拮抗剂，在中枢神经系统细胞培养中竞争性地抑制VIP结合并阻断VIP介导的功能，也会产生性能损害。通过与VIP共同治疗，这种迟滞被减弱，支持观察到的损伤的特异性。因此，gp120和VIP拮抗剂产生相似的空间辨别迟缓，提示两者都可能损害空间相关刺激控制的记忆。
The external envelope glycoprotein (gp120) of the human immunodeficiency virus (HIV) has been shown to be toxic to neurons in culture. To further investigate the neurological effects of gp120, the involvement of this protein with the acquisition of spatial discrimination was assessed. Both native and recombinant gp120 were administered into the cerebral ventricles of adult rats and performance was evaluated in the Morris swim maze. Gp120 treatment retarded acquisition after daily administration of 12 ng. The specificity of this impairment was demonstrated in that the performance of animals given the same amount of gp160 from recombinant baculovirus was not different from animals given saline. Vasoactive intestinal peptide (VIP) has been shown to block gp120-induced neurotoxicity in culture and a VIP receptor antagonist has displayed toxic properties to neurons in culture. We show here that this antagonist, which competitively inhibits VIP binding and blocks VIP-mediated functions in cell cultures from the CNS, also produced an impairment of performance. This retardation was attenuated by cotreatment with VIP, supporting the specificity of the observed impairment. Thus, gp120 and the VIP antagonist produced similar retardation of spatial discrimination, suggesting that both may impair memory for spatially related stimulus control.