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发育期Long Evans大鼠海马和前扣带回皮质中GluA1和GluA2 AMPA受体亚型分布的研究。

Investigation of GluA1 and GluA2 AMPA receptor subtype distribution in the hippocampus and anterior cingulate cortex of Long Evans rats during development.

作者信息

Tzakis Nikolaos, Holahan Matthew R

机构信息

Department of Neuroscience, Carleton University, 1125 Colonel by Drive, Ottawa, Ontario, K1S 5B6, Canada.

出版信息

IBRO Rep. 2020 Apr 3;8:91-100. doi: 10.1016/j.ibror.2020.03.003. eCollection 2020 Jun.

Abstract

Preadolescent development is characterized by a reorganization of connectivity within and between brain regions that coincides with the emergence of complex behaviors. During the preadolescent period, the rodent hippocampus and regions of the frontal cortex are remodelled as the brain strengthens active connections and eliminates others. In the developing and mature brain, changes in the properties of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAr)-mediated synaptic responses contribute to experience-dependent changes in neural organization and function. AMPAr are made up of 4 subunits, of which GluA1 and GluA2 have been shown to play the most prominent role in functional plasticity. In this study, we sought to determine whether levels of these two subunits changed during the course of pre-adolescent development in the hippocampus and anterior cingulate cortex (ACC). To investigate the developmental changes in GluA1 and GluA2 AMPAr subunits, Western blotting and immunohistochemistry were performed on the ACC and hippocampus from P18 - P30 and compared to adult (P50) levels and distribution. Within the hippocampus, protein levels of GluA1 and GluA2 peaked around P26-30 whereby localized staining in the dentate gyrus reflected this pattern. GluA1 and GluA2 levels within the ACC showed little variation during this developmental period. These results indicate that changes in AMPAr subunits within the hippocampus coincide with developmental modifications that underlie the shift from juvenile- to adult-like capabilities. However, changes in AMPAr distribution in the ACC might not mediate changes that reflect preadolescent developmental shifts.

摘要

青春期前的发育特征是大脑区域内部和之间的连接性重新组织,这与复杂行为的出现同时发生。在青春期前阶段,随着大脑加强活跃连接并消除其他连接,啮齿动物的海马体和额叶皮质区域会发生重塑。在发育中和成熟的大脑中,α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAr)介导的突触反应特性的变化有助于神经组织和功能的经验依赖性变化。AMPAr由4个亚基组成,其中GluA1和GluA2在功能可塑性中发挥着最突出的作用。在本研究中,我们试图确定这两个亚基的水平在海马体和前扣带回皮质(ACC)的青春期前发育过程中是否发生变化。为了研究GluA1和GluA2 AMPAr亚基的发育变化,对P18 - P30的ACC和海马体进行了蛋白质印迹和免疫组织化学分析,并与成年(P50)水平和分布进行了比较。在海马体内,GluA1和GluA2的蛋白质水平在P26 - 30左右达到峰值,齿状回中的局部染色反映了这种模式。在此发育期间,ACC内的GluA1和GluA2水平变化不大。这些结果表明,海马体内AMPAr亚基的变化与从幼年到成年样能力转变所依据的发育变化相一致。然而,ACC中AMPAr分布的变化可能不会介导反映青春期前发育转变的变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf2f/7152689/48e204a42faa/gr1.jpg

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