Abstract:
The excitatory-inhibitory imbalance has been considered an important mechanism underlying stress-related psychiatric disorders. In the present study, rats were exposed to 6 days of inescapable foot shock (IFS) to induce stress. The open field test and elevated plus maze test showed that IFS-exposed rats exhibited increased anxiety-like behavior. Immunofluorescence showed that IFS rats had a decreased density of GAD67-immunoreactive interneurons in the dorsal hippocampal CA1 region, while no significant change in the density of CaMKIIα-immunoreactive glutamatergic neurons was seen. We investigated the expression of different interneuron subtype markers, including parvalbumin (PV), somatostatin (SST), and calretinin (CR), and noted a marked decline in the density of PV-immunoreactive interneurons in the dorsal CA1 region of IFS rats. The perineuronal net (PNN) is a specialized extracellular matrix structure primarily around PV interneurons. We used Wisteria floribunda agglutinin lectin to label the PNNs and observed that IFS rats had an increased proportion of PNN-coated PV-positive interneurons in CA1. The number of PSD95-positive excitatory synaptic puncta on the soma of PNN-free PV-positive interneurons was significantly higher than that of PNN-coated PV-positive interneurons. Our findings suggest that the effect of IFS on the hippocampal GABAergic interneurons could be cell-type-specific. Loss of PV phenotype in the dorsal hippocampal CA1 region may contribute to anxiety in rats. The dysregulated PV-PNN relationship in CA1 after traumatic stress exposure might represent one of the neurobiological correlates of the observed anxiety-like behavior.
摘要:
兴奋性-抑制性失衡被认为是与压力相关的精神疾病的重要机制。在本研究中,将大鼠暴露于6天的不可避免的足休克(IFS)以诱导应激。野外试验和高架迷宫试验表明,暴露于IFS的大鼠表现出焦虑样行为增加。免疫荧光显示IFS大鼠背侧海马CA1区GAD67免疫反应性中间神经元密度降低,而CaMKIIα-免疫反应性谷氨酸能神经元的密度没有明显变化。我们研究了不同中间神经元亚型标记的表达,包括小白蛋白(PV),生长抑素(SST),和calretinin(CR),并注意到IFS大鼠背侧CA1区域PV免疫反应性中间神经元的密度显着下降。神经周网(PNN)是主要围绕PV中间神经元的专门的细胞外基质结构。我们使用紫藤花凝集素来标记PNN,并观察到IFS大鼠在CA1中PNN包被的PV阳性中间神经元的比例增加。无PNN的PV阳性中间神经元的体细胞上PSD95阳性兴奋性突触小点的数量显着高于PNN包被的PV阳性中间神经元。我们的发现表明,IFS对海马GABA能中间神经元的影响可能是细胞类型特异性的。背侧海马CA1区PV表型的丧失可能导致大鼠焦虑。创伤应激暴露后CA1中异常调节的PV-PNN关系可能代表观察到的焦虑样行为的神经生物学相关因素之一。