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母体剥夺导致大鼠内侧前额叶皮层的时间记忆和认知灵活性缺陷,并夸大突触可塑性。

Maternal deprivation induces deficits in temporal memory and cognitive flexibility and exaggerates synaptic plasticity in the rat medial prefrontal cortex.

机构信息

INSERM, UMRs, Physiopathologie des Maladies du Système Nerveux Central, Paris, France.

出版信息

Neurobiol Learn Mem. 2012 Oct;98(3):207-14. doi: 10.1016/j.nlm.2012.08.004. Epub 2012 Aug 24.

Abstract

Early life adverse events can lead to structural and functional impairments in the prefrontal cortex (PFC). Here, we investigated whether maternal deprivation (MD) alters PFC-dependent executive functions, neurons and astrocytes number and synaptic plasticity in adult male Long-Evans rats. The deprivation protocol consisted of a daily separation of newborn Long-Evans pups from their mothers and littermates 3h/day postnatal day 1-14. Cognitive performances were assessed in adulthood using the temporal order memory task (TMT) and the attentional set-shifting task (ASST) that principally implicates the PFC and the Morris water maze task (WMT) that does not essentially rely on the PFC. The neurons and astrocytes of the prelimbic (PrL) area of the medial PFC (mPFC) were immunolabelled respectively with anti-NeuN and anti-GFAP antibodies and quantified by stereology. The field potentials evoked by electrical stimulation of ventral hippocampus (ventral HPC) were recorded in vivo in the PrL area. In adulthood, MD produced cognitive deficits in two PFC-dependent tasks, the TMT and ASST, but not in the WMT. In parallel, MD induced in the prelimbic area of the medial PFC an upregulation of long-term potentiation (LTP), without any change in the number of neurons and astrocytes. We provide evidence that MD leads in adults to an alteration of the cognitive abilities dependent on the PFC, and to an exaggerated synaptic plasticity in this region. We suggest that this latter phenomenon may contribute to the impairments in the cognitive tasks.

摘要

早期生活中的不良事件可导致前额叶皮层(PFC)的结构和功能损伤。在这里,我们研究了母体剥夺(MD)是否会改变成年雄性 Long-Evans 大鼠的 PFC 依赖的执行功能、神经元和星形胶质细胞数量以及突触可塑性。剥夺方案包括在出生后第 1-14 天每天将新生 Long-Evans 幼崽与其母亲和同窝幼崽分离 3 小时。在成年期使用时间顺序记忆任务(TMT)和注意力定势转移任务(ASST)评估认知表现,这主要涉及 PFC,以及不主要依赖 PFC 的 Morris 水迷宫任务(WMT)。内侧前额叶皮质(mPFC)的前额叶(PrL)区域的神经元和星形胶质细胞分别用抗 NeuN 和抗 GFAP 抗体免疫标记,并通过立体学进行定量。通过电刺激腹侧海马(ventral HPC)在体内记录 PrL 区域的场电位。在成年期,MD 在两个依赖 PFC 的任务(TMT 和 ASST)中引起认知缺陷,但在 WMT 中没有。同时,MD 在 mPFC 的 PrL 区诱导长时程增强(LTP)的上调,而神经元和星形胶质细胞的数量没有变化。我们提供的证据表明,MD 导致成年人大脑依赖于 PFC 的认知能力改变,并导致该区域的突触可塑性增强。我们认为,后一种现象可能导致认知任务受损。

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