Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala.
Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala.
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DOI：
10.1016/j.bbi.2016.01.020
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Mocchetti I
中科院分区：
文献类型：
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作者：
Bachis A;Forcelli P;Masliah E;Campbell L;Mocchetti I
人类免疫缺陷病毒1型（HIV）感染的大脑产生认知和运动障碍。此外，HIV阳性个体表现出行为改变，如冷漠，自发性或情绪反应减少，通常见于焦虑症。焦虑会导致心理压力，这已被证明会影响艾滋病毒疾病的进展。这些考虑强调了确定HIV中的焦虑是否纯粹是心理社会的重要性，或者相反，是否存在与HIV感染直接相关的分子级联，可能介导焦虑。本研究有两个目标：1）确定长期暴露于病毒蛋白是否会在动物模型中诱导焦虑样行为，2）确定这种暴露是否会导致解剖学异常，从而解释焦虑增加。我们使用了gp120转基因小鼠，这些小鼠表现出与具有认知和运动障碍的HIV阳性受试者相似的行为和分子缺陷。与野生型小鼠相比，6个月大的gp120转基因小鼠表现出焦虑样行为，通过旷场、明/暗转换任务和前脉冲抑制测试测量。此外，与年龄匹配的野生型相比，gp120转基因小鼠杏仁核中的棘数量增加，脑源性神经营养因子和组织纤溶酶原激活物水平也更高。我们的数据支持这一假设，即艾滋病毒，通过gp120，可能会导致杏仁核的结构变化，导致适应不良的焦虑反应。
Human immunodeficiency virus type 1 (HIV) infection of the brain produces cognitive and motor disorders. In addition, HIV positive individuals exhibit behavioral alterations, such as apathy, and a decrease in spontaneity or emotional responses, typically seen in anxiety disorders. Anxiety can lead to psychological stress, which has been shown to influence HIV disease progression. These considerations underscore the importance of determining if anxiety in HIV is purely psychosocial, or if by contrast, there are the molecular cascades associated directly with HIV infection that may mediate anxiety. The present study had two goals: 1) to determine if chronic exposure to viral proteins would induce anxiety-like behavior in an animal model and 2) to determine if this exposure results in anatomical abnormalities that could explain increased anxiety. We have used gp120 transgenic mice, which display behavior and molecular deficiencies similar to HIV positive subjects with cognitive and motor impairments. In comparison to wild type mice, 6 months old gp120 transgenic mice demonstrated an anxiety like behavior measured by open field, light/dark transition task, and prepulse inhibition tests. Moreover, gp120 transgenic mice have an increased number of spines in the amygdala, as well as higher levels of brain-derived neurotrophic factor and tissue plasminogen activator when compared to age-matched wild type. Our data support the hypothesis that HIV, through gp120, may cause structural changes in the amygdala that lead to maladaptive responses to anxiety.