Conditioned taste aversion memory extinction temporally induces insular cortical BDNF release and inhibits neuronal apoptosis
Conditioned taste aversion memory extinction temporally induces insular cortical BDNF release and inhibits neuronal apoptosis
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条件性味觉厌恶记忆消退暂时诱导岛叶皮质 BDNF 释放并抑制神经元凋亡
DOI：
10.2147/ndt.s215289
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发表时间：
2019-08
影响因子：
3.2
通讯作者：
王云彦
中科院分区：
文献类型：
--
作者：
刘殿玮;马玲;张旭华;王云彦
背景记忆消失与精神障碍有关，如创伤后应激障碍(PTSD)。脑源性神经营养因子(BDNF)的分泌和合成通过激活原肌球蛋白相关的激酶B(TrkB)受体来调节各种记忆过程。然而，记忆消失是否在其定位的基础上诱导了脑源性神经营养因子的合成和分泌，目前还不清楚。在这项研究中，我们旨在研究在条件性味觉厌恶(CTA)记忆消失的背景下，岛叶皮质(IC)活动依赖的BDNF的分泌和合成。材料与方法建立大鼠CTA记忆消退模型，消退实验后即刻向IC内注入等量BDNF抗体(或等量载体)。采用实时荧光定量聚合酶链式反应和原位杂交技术检测脑源性神经营养因子、神经生长因子和神经营养因子4的基因表达。采用酶联免疫吸附试验检测脑源性神经营养因子的蛋白水平。此外，用免疫沉淀和免疫印迹法评估磷酸化TrkB与总TrkB的水平。Western blotting检测c-Fos、总细胞外信号调节蛋白(ERK)、磷酸化ERK和凋亡相关蛋白(caspase-3)的表达。结果我们发现阻断IC内的BDNF信号干扰了CTA的消退，提示IC内的BDNF信号是CTA消退所必需的。C-Fos表达水平的升高表明在CTA消退过程中诱导了IC内神经元的活动。此外，在灭绝过程中，IC内BDNF的基因表达和蛋白水平的时间变化也被注意到。此外，我们发现TrkB的磷酸化在BDNF表达增强之前增加，这表明CTA消退诱导IC中快速分泌活性依赖的BDNF。最后，我们发现在CTA消退后，Caspase-3在IC中的表达降低。结论CTA记忆消失可在一定时间内诱导脑内脑源性神经营养因子的释放和合成，并抑制神经元的凋亡。
Background Memory extinction has been reported to be related to psychiatric disorders, such as post-traumatic stress disorder (PTSD). Secretion and synthesis of brain-derived neurotrophic factor (BDNF) have been shown to temporally regulate various memory processes via activation of tropomyosin-related kinase B (TrkB) receptors. However, whether memory extinction induces the synthesis and secretion of BDNF on the basis of its localization is not understood. In this study, we aim to investigate activity-dependent BDNF secretion and synthesis in the insular cortex (IC) in the setting of conditioned taste aversion (CTA) memory extinction. Materials and methods Rats were subjected to CTA memory extinction and BDNF antibody (or the equal volume of vehicle) was microinjected into the IC immediately after the extinction testing. Real-time polymerase chain reaction and in situ hybridization were used to detect the gene expression of BDNF, NGF and NT4. The protein levels of BDNF were determined through the enzyme-linked immunosorbent assay. In addition, the levels of phosphorylated TrkB normalized to total TrkB were evaluated using immunoprecipitation and immunoblotting. c-Fos, total extracellular signal-regulated kinase (Erk), phosphorylated Erk, and apoptosis-related protein (caspase-3), were detected by Western blotting. Results We found that blocking BDNF signaling within the IC disrupts CTA extinction, suggesting that BDNF signaling in the IC is necessary for CTA extinction. Increased expression levels of c-Fos indicate the induced neuronal activity in the IC during CTA extinction. In addition, temporal changes in the gene expression and protein levels of BDNF in the IC were noted during extinction. Moreover, we found that phosphorylation of TrkB increased prior to the enhanced BDNF expression, suggesting that CTA extinction induces rapid activity-dependent BDNF secretion in the IC. Finally, we found decreased expression of caspase-3 in the IC after CTA extinction. Conclusion These results demonstrate that CTA memory extinction temporally induces the release and synthesis of BDNF in the IC and inhibits neuronal apoptosis.
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影响因子：
16.2
作者：
Park, Hyungju;Popescu, Andrei;Poo, Mu-ming
通讯作者：
Poo, Mu-ming
BDNF 信号传导从基底外侧杏仁核到边缘下前额皮质的传递参与条件性味觉厌恶消退
影响因子：
5.3
作者：
Yu, Hui;Wang, Yue;Kong, Liang;Chen, Zhe-Yu
通讯作者：
Chen, Zhe-Yu
影响因子：
56.9
作者：
Berman, DE;Dudai, Y
通讯作者：
Dudai, Y
影响因子：
3.3
作者：
Huang, Niannian;Yang, Chun;Xu, Hui
通讯作者：
Xu, Hui
影响因子：
7.6
作者：
Rosas-Vidal, Luis E.;Do-Monte, Fabricio H.;Quirk, Gregory J.
通讯作者：
Quirk, Gregory J.