Blockade of protein phosphatase 2B activity in the amygdala increases anxiety- and depression-like behaviors in mice.
Blockade of protein phosphatase 2B activity in the amygdala increases anxiety- and depression-like behaviors in mice.
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DOI：
10.1016/j.biopsych.2009.07.004
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发表时间：
2009-12-15
影响因子：
10.6
通讯作者：
Picciotto MR
中科院分区：
文献类型：
--
作者：
Bahi A;Mineur YS;Picciotto MR
器官移植患者接受钙调磷酸酶抑制剂环孢素- a （CsA）的慢性管理，并显示情绪障碍的发生率增加。通过免疫组织化学可以在杏仁核中观察到显著的钙调磷酸酶表达，杏仁核是与情绪障碍和焦虑相关的行为重要的大脑区域。因此，确定慢性钙调磷酸酶阻断是否可能导致这些患者的焦虑和抑郁症状是很重要的。采用药理学（CsA）和病毒介导的基因转移（腺相关shRNA病毒表达（AAV-shRNA））方法全面和选择性地抑制小鼠大脑杏仁核中的钙调磷酸酶活性，以确定钙调磷酸酶在抑郁和焦虑相关行为中的作用。使用CsA系统抑制钙调神经磷酸酶活性或使用aav递送的靶向钙调神经磷酸酶A的短发卡rna局部下调杏仁核钙调神经磷酸酶水平，增加了升高+迷宫和光/暗测试中焦虑的行为测量，但运动活动没有变化。在强迫游泳和悬尾的抑郁样行为模型中，杏仁核中的钙调磷酸酶阻断增加了不动性，类似于导致抑郁样表型的操作。综上所述，这些数据表明，杏仁核中钙调磷酸酶活性的降低会增加焦虑和抑郁样行为。这些研究表明，对器官移植患者长期给予CsA可能对焦虑和情绪有显著影响，这应该被认为是预防移植排斥反应治疗的临床结果。
Organ transplant patients receive chronic administration of the calcineurin inhibitor Cyclosporin-A (CsA) and demonstrate increased incidence of mood disorders. Significant calcineurin expression can be observed using immunohistochemistry in the amygdala, a brain area important for behaviors related to mood disorders and anxiety. It is therefore important to determine whether chronic blockade of calcineurin may contribute to symptoms of anxiety and depression in these patients. Pharmacological (CsA) and viral-mediated gene transfer (adeno-associated viral expression of shRNA (AAV-shRNA)) approaches were used to inhibit calcineurin activity globally and selectively in the amygdala of the mouse brain to determine the role of calcineurin in behaviors related to depression and anxiety. Systemic inhibition of calcineurin activity with CsA or local down-regulation of calcineurin levels in the amygdala using AAV-delivered short hairpin RNAs targeting calcineurin A increased behavioral measures of anxiety in both the elevated plus maze and light/dark tests with no changes in locomotor activity. In the forced swim and tail suspension models of depression-like behavior, calcineurin blockade in the amygdala increased immobility similar to manipulations that lead to a depression-like phenotype. Taken together, these data demonstrate that decreasing calcineurin activity in the amygdala increases anxiety- and depression-like behaviors. These studies suggest that chronic administration of CsA to organ transplant patients could have significant effects on anxiety and mood and that this should be recognized as a clinical consequence of treatment to prevent transplant rejection.
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影响因子：
3.4
作者：
Bahi, A;Boyer, F;Dreyer, JL
通讯作者：
Dreyer, JL
影响因子：
158.5
作者：
DEGROEN, PC;AKSAMIT, AJ;KROM, RAF
通讯作者：
KROM, RAF
影响因子：
82.9
作者：
Hommel, JD;Sears, RM;DiLeone, RJ
通讯作者：
DiLeone, RJ
影响因子：
3.3
作者：
Crozatier, C.;Farley, S.;Tzavara, E. T.
通讯作者：
Tzavara, E. T.
影响因子：
4.7
作者：
Mineur, Yann S.;Somenzi, Oli;Picciotto, Marina R.
通讯作者：
Picciotto, Marina R.