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反复的新生期分离应激会改变啮齿动物齿状回和基底外侧杏仁核中神经化学特征化的中间神经元亚群的组成。

Repeated neonatal separation stress alters the composition of neurochemically characterized interneuron subpopulations in the rodent dentate gyrus and basolateral amygdala.

作者信息

Seidel Katja, Helmeke Carina, Poeggel Gerd, Braun Katharina

机构信息

Institute for Biology, Department of Zoology/Developmental Neurobiology, Otto-von-Guericke University, 39118 Magdeburg, Germany.

出版信息

Dev Neurobiol. 2008 Aug;68(9):1137-52. doi: 10.1002/dneu.20651.

Abstract

Emotional experience during early life has been shown to interfere with the development of excitatory synaptic networks in the prefrontal cortex, hippocampus, and the amygdala of rodents and primates. The aim of the present study was to investigate a developmental "homoeostatic synaptic plasticity" hypothesis and to test whether stress-induced changes of excitatory synaptic composition are counterbalanced by parallel changes of inhibitory synaptic networks. The impact of repeated early separation stress on the development of two GABAergic neuronal subpopulations was quantitatively analyzed in the brain of the semiprecocial rodent Octodon degus. Assuming that PARV- and CaBP-D28k-expression are negatively correlated to the level of inhibitory activity, the previously described reduced density of excitatory spine synapses in the dentate gyrus of stressed animals appears to be "amplified" by elevated GABAergic inhibition, reflected by reduced PARV- (down to 85%) and CaBP-D28k-immunoreactivity (down to 74%). In opposite direction, the previously observed elevated excitatory spine density in the CA1 region of stressed animals appears to be amplified by reduced inhibition, reflected by elevated CaPB-D28k-immunoreactivity (up to 149%). In the (baso)lateral amygdala, the previously described reduction of excitatory spine synapses appears to be "compensated" by reduced inhibitory activity, reflected by dramatically elevated PARV- (up to 395%) and CaPB-D28k-immunoreactivity (up to 327%). No significant differences were found in the central nucleus of the amygdala, the piriform, and somatosensory cortices and in the hypothalamic paraventricular nucleus. Thus during stress-evoked neuronal and synaptic reorganization, a homeostatic balance between excitation and inhibition is not maintained in all regions of the juvenile brain.

摘要

早期生活中的情感体验已被证明会干扰啮齿动物和灵长类动物前额叶皮质、海马体和杏仁核中兴奋性突触网络的发育。本研究的目的是探讨一种发育性“稳态突触可塑性”假说,并测试应激诱导的兴奋性突触组成变化是否会被抑制性突触网络的平行变化所抵消。在半早熟啮齿动物八齿鼠的大脑中,定量分析了反复早期分离应激对两个γ-氨基丁酸能神经元亚群发育的影响。假设小白蛋白(PARV)和钙结合蛋白D28k(CaBP-D28k)的表达与抑制活性水平呈负相关,应激动物齿状回中先前描述的兴奋性棘突突触密度降低似乎因γ-氨基丁酸能抑制作用增强而“放大”,这表现为PARV免疫反应性降低(降至85%)和CaBP-D28k免疫反应性降低(降至74%)。相反,应激动物CA1区先前观察到的兴奋性棘突密度升高似乎因抑制作用减弱而“放大”,表现为CaPB-D28k免疫反应性升高(高达149%)。在(基底)外侧杏仁核中,先前描述的兴奋性棘突突触减少似乎因抑制活性降低而“得到补偿”,表现为PARV免疫反应性显著升高(高达395%)和CaPB-D28k免疫反应性显著升高(高达327%)。在杏仁核中央核、梨状皮质、躯体感觉皮质和下丘脑室旁核中未发现显著差异。因此,在应激诱发的神经元和突触重组过程中,幼龄大脑的所有区域并非都能维持兴奋与抑制之间的稳态平衡。

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