Effects of chronic immobilization stress on anxiety-like behavior and basolateral amygdala morphology in Fmr1 knockout mice.

Effects of chronic immobilization stress on anxiety-like behavior and basolateral amygdala morphology in Fmr1 knockout mice.
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DOI:
10.1016/j.neuroscience.2011.06.047
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发表时间:
2011-10-27
期刊:
影响因子:
3.3
通讯作者:
Smith, C. B.
Smith, C. B.
中科院分区:
医学3区
文献类型:
--
作者:
Qin, M.;Xia, Z.;Huang, T.;Smith, C. B.

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一些临床证据支持脆性X综合征(FXS)可能涉及下丘脑-垂体-肾上腺轴功能失调的观点。我们在FXS(Fmr1 KO)小鼠模型中测试了这一想法,发现对急性应激的激素反应与野生型(WT)小鼠相似。我们报道了Fmr1KO小鼠对慢性应激(CS)的反应。在连续10天每天120分钟的束缚后,我们评估了基底外侧杏仁核(BLA)的树突和棘突的形态。我们还监测了在高架加迷宫(EPM)中的行为和对这种新的空间环境的激素反应。CS后,两种基因型的小鼠都出现了肾上腺肥大,但WT小鼠的影响更大。EPM中的行为表明,只有WT小鼠在CS后焦虑程度有预期的增加。血清皮质酮和ACTH水平均随着EPM空间新颖性的增加而升高,但不同基因型之间的激素反应没有差异。在WT小鼠中,BLA树突状分支在胞体附近增加,而在Fmr1KO小鼠中,分支在胞体附近未受影响,在胞体远端的一点略有减少。类似地,WT小鼠顶端和底部树突上的棘突密度增加,而Fmr1 KO小鼠的棘突密度降低。WT小鼠顶端和基底部树突上的棘突长度增加,但Fmr1 KO小鼠不受影响。这些行为反应的差异和对BLA神经元形态的影响表明Fmr1 KO小鼠的适应性反应减弱。
Several lines of clinical evidence support the idea that fragile X syndrome (FXS) may involve a dysregulation of hypothalamic-pituitary-adrenal axis function. We had tested this idea in a mouse model of FXS (Fmr1 KO) and found that the hormonal response to acute stress was similar to that of wild type (WT) mice. We report here responses to chronic stress (CS) in Fmr1 KO mice. Following restraint for 120 min/day, 10 consecutive days, we assessed dendrite and spine morphology in basolateral amygdala (BLA). We also monitored behavior in an elevated plus maze (EPM) and the hormonal response to this novel spatial environment. After CS, mice of both genotypes underwent adrenal hypertrophy, but effects were greater in WT mice. Behavior in the EPM indicated that only WT mice had the expected increase in anxiety following CS. Serum corticosterone and ACTH levels were both increased following the spatial novelty of EPM, and there were no differences between genotypes in the hormonal responses. BLA dendritic branching increased proximal to the soma in WT, but in Fmr1 KO mice branching was unaffected close to the soma and slightly decreased at one point distal to the soma. Similarly, spine density on apical and basal dendrites increased in WT but decreased in Fmr1 KO mice. Spine length on apical and basal dendrites increased in WT but was unaffected in Fmr1 KO mice. These differences in behavioral response and effects on neuron morphology in BLA suggest a diminished adaptive response of Fmr1 KO mice.
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