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嗜酒大鼠和非嗜酒大鼠在终纹床核杏仁核扩展区各区域中脑源性神经营养因子表达的固有差异。

Innate differences in the expression of brain-derived neurotrophic factor in the regions within the extended amygdala between alcohol preferring and nonpreferring rats.

作者信息

Prakash Anand, Zhang Huaibo, Pandey Subhash C

机构信息

Department of Psychiatry, University of Illinois at Chicago, Jesse Brown VA Medical Center, Chicago, Illinois 60612, USA.

出版信息

Alcohol Clin Exp Res. 2008 Jun;32(6):909-20. doi: 10.1111/j.1530-0277.2008.00650.x. Epub 2008 Apr 26.

Abstract

BACKGROUND

Animal lines such as alcohol-preferring (P) and nonpreferring (NP) rats appear to be suitable animal models to investigate the biological basis of alcohol-drinking behaviors. The extended amygdala serves as a neuroanatomical substrate for alcohol-drinking behaviors. Brain-derived neurotrophic factor (BDNF) in the amygdala has been implicated in alcohol-drinking behaviors; however, its expression in the extended amygdala of P and NP rats is unknown. Therefore, we examined the basal expression of BDNF in the extended amygdala of alcohol naive P and NP rats.

METHODS

We determined the basal mRNA and protein levels of BDNF by in situ RT-PCR and immuno-histochemical procedure, respectively, in the amygdaloid [central nucleus of amygdala (CeA), medial nucleus of amygdala (MeA), and basolateral amygdala (BLA)], nucleus accumbal (NAc shell and core), and bed nucleus of stria terminalis (BNST) [lateral BNST (lBNST), medial BNST (mBNST), and ventral BNST (vBNST)] brain structures of P and NP rats. In addition, we examined the localization of BDNF in neurons using double-immunofluorescence labeling of BDNF with neuron-specific nuclear protein (NeuN) and also determined the number of NeuN-positive neurons in the amygdaloid structures of P and NP rats.

RESULTS

The mRNA and protein levels of BDNF were found to be significantly lower in both the CeA and MeA, but not in the BLA, of P compared with NP rats. We also found that BDNF was expressed in neurons in the amygdaloid structures of P and NP rats. In addition, we found that the number of NeuN-positive neurons was similar in the amygdaloid structures of P and NP rats. Interestingly, the mRNA and protein levels of BDNF were also significantly lower in the lBNST, mBNST, and vBNST of P compared with NP rats. On the other hand, mRNA and protein levels of BDNF were similar in the NAc shell and core structures of P and NP rats.

CONCLUSIONS

P and NP rats are selectively bred for higher and lower alcohol preference, respectively; therefore it is possible that lower BDNF levels in the amygdaloid and BNST structures may be associated with the excessive alcohol-drinking behaviors of P rats.

摘要

背景

诸如嗜酒(P)和不嗜酒(NP)大鼠等动物品系似乎是研究饮酒行为生物学基础的合适动物模型。扩展杏仁核是饮酒行为的神经解剖学基础。杏仁核中的脑源性神经营养因子(BDNF)与饮酒行为有关;然而,其在P和NP大鼠扩展杏仁核中的表达尚不清楚。因此,我们检测了未接触过酒精的P和NP大鼠扩展杏仁核中BDNF的基础表达。

方法

我们分别通过原位逆转录聚合酶链反应(RT-PCR)和免疫组织化学方法,测定了P和NP大鼠杏仁核[杏仁核中央核(CeA)、杏仁核内侧核(MeA)和杏仁核基底外侧核(BLA)]、伏隔核(NAc壳和核心)以及终纹床核(BNST)[外侧BNST(lBNST)、内侧BNST(mBNST)和腹侧BNST(vBNST)]脑区中BDNF的基础mRNA和蛋白水平。此外,我们使用BDNF与神经元特异性核蛋白(NeuN)的双重免疫荧光标记来检测BDNF在神经元中的定位,并确定P和NP大鼠杏仁核结构中NeuN阳性神经元的数量。

结果

与NP大鼠相比,P大鼠的CeA和MeA中BDNF的mRNA和蛋白水平均显著降低,但BLA中未降低。我们还发现P和NP大鼠杏仁核结构中的神经元表达BDNF。此外,我们发现P和NP大鼠杏仁核结构中NeuN阳性神经元的数量相似。有趣的是,与NP大鼠相比,P大鼠的lBNST、mBNST和vBNST中BDNF的mRNA和蛋白水平也显著降低。另一方面,P和NP大鼠的NAc壳和核心结构中BDNF的mRNA和蛋白水平相似。

结论

P和NP大鼠分别因对酒精的偏好较高和较低而进行选择性培育;因此,杏仁核和BNST结构中较低的BDNF水平可能与P大鼠的过度饮酒行为有关。

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