Neonatal intrahippocampal injection of the HIV-1 proteins gp120 and Tat: Differential effects on behavior and the relationship to stereological hippocampal measures
Neonatal intrahippocampal injection of the HIV-1 proteins gp120 and Tat: Differential effects on behavior and the relationship to stereological hippocampal measures
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DOI：
10.1016/j.brainres.2008.07.032
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发表时间：
2008-09-26
期刊：
影响因子：
2.9
通讯作者：
Mactutus, Charles F.
中科院分区：
文献类型：
--
作者：
Fitting, Sylvia;Booze, Rosemarie M.;Mactutus, Charles F.
HIV-1蛋白，如Tat和gp120，被认为在获得性免疫缺陷综合征(AIDS)的中枢神经系统(CNS)病理中发挥关键作用。本研究试图确定TAT和/或gp120在行为发育中的潜在作用，以及与HIV-1蛋白对大鼠海马区的长期影响的关系。在出生后第1天对13窝雄性SD仔猪进行双侧注射，每窝1只，分别用于4个处理条件：VEH(0.5亩L无菌缓冲液)、Gp12 0(10 0 Ng)、TAT(2 5 Mgg)或gp12 0+TAT(10 0 ng+2 5 mg)。体重没有受到任何一种蛋白质处理的影响。TAT揭示了在发育早期的许多行为评估以及成年后对注意力前期过程和空间记忆的短暂影响。Gp120对负地趋性(P8-P10)和运动活动(P94-P96)具有更强的选择性。Gp120+Tat的联合效应在睁开眼睛方面与gp120和Tat在负向趋地性上潜在的交互作用被注意到。在大约7个半月龄时，用基于设计的体视学方法对海马区的5个亚区[颗粒层(GL)、齿状回门区(DGH)、杏仁角(CA)2/3、CA1和下丘(SUB)]的细胞总数进行了解剖学评估[Fitting，S.，Booze，R.M.，Hasselrot，U，Mactutus，C.F.，2007a。HIV-1蛋白在大鼠海马区的不同长期神经毒性：一项基于设计的体视学研究。海马体18(2)，135-147]。通过简单的回归分析，表明了成人海马区早期反射发育与估计细胞数之间的关系。此外，DGH内神经元和星形胶质细胞的估计数量解释了探测测试中搜索行为分布的81%的变异。总之，这些数据表明，DGH可能参与了由于新生儿暴露于HIV-1蛋白而导致的成年后空间记忆的改变。(C)2008爱思唯尔B.V.保留所有权利。
HIV-1 proteins, such as Tat and gp120, are believed to play a crucial role in the central nervous system (CNS) pathology of acquired immune deficiency syndrome (AIDS). The present study sought to determine the potential role of Tat and/or gp120 on behavioral development and the relationship to the long-term effects of the HIV-1 proteins on the rat hippocampus. Male pups of 13 Sprague-Dawley litters were bilaterally injected on postnatal day (P)I. Every litter contributed an animal to each of four treatment condition: VEH (0.5 mu l sterile buffer), gp120 (100 ng), Tat (25 mu g) or combined gp120+Tat (100 ng+25 mu g). Body weight was not affected by either protein treatment. Tat revealed a transient effect on many of the behavioral assessments early in development as well as on preattentive processes and spatial memory in adulthood. Gp120 had more selective effects on negative geotaxis (P8-P10) and on locomotor activity (P94-P96). Combined gp120+Tat effects were noted for eye opening with potential interactive effects of gp120 and Tat on negative geotaxis. Anatomical assessment at similar to 7 1/2 months of age was conducted by using design-based stereology to quantify the total cell number in five hippocampal subregions [granule layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB)] [Fitting, S., Booze, R.M., Hasselrot, U., Mactutus, C.F., 2007a. Differential long-term neurotoxicity of HIV-1 proteins in the rat hippocampal formation: a design-based stereological study. Hippocampus 18(2), 135-147]. A relationship between early reflex development and estimated cell number in the adult hippocampus was indicated by simple regression analyses. In addition, estimated number of neurons and astrocytes in the DGH explained 81% of the variance of the distribution of searching behavior in the probe test. Collectively, these data indicate that the DGH may participate in the spatial memory alterations observed in adulthood consequent to neonatal exposure to HIV-1 proteins. (C) 2008 Elsevier B.V. All rights reserved.