Laboratory of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia.
Neuropsychobiology. 2012;66(2):112-9. doi: 10.1159/000338605. Epub 2012 Jul 17.
Chronic stress is a contributing risk factor in the development of psychiatric illnesses, including depressive disorders. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in the brain plasticity. Previously, we investigated the effects of chronic social stress in the limbic brain structures of Wistar rats (hippocampus, HIPPO, and prefrontal cortex, PFC) and found multiple characteristics that resembled alterations described in some clinical studies of depression. We extended our investigations and followed the behavior of stressed animals by the open field test (OFT) and forced swimming test (FST), and the expression and polysialylation of synaptic plasticity markers, neural cell adhesion molecule (NCAM) and L1, in the HIPPO and PFC. We also determined the adrenal gland mass and plasma corticosterone (CORT) as a terminal part of the hypothalamic-pituitary-adrenal axis activity. Our data indicated that stressed animals avoided the central zone in the OFT and displayed decreased swimming, but prolonged immobility in the FST. The animals exhibited marked hypertrophy of the adrenal gland cortex, in spite of decreased serum CORT. Simultaneously, the stressed animals exhibited an increase in NCAM mRNA expression in the HIPPO, but not in the PFC. The synaptosomal NCAM of the HIPPO was markedly polysialylated, while cortical PSA-NCAM was significantly decreased. The results showed that chronic social isolation of Wistar rats causes both anxiety-like and depression-like behavior. These alterations are parallel with molecular changes in the limbic brain, including diminished NCAM sialylation in the PFC. Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology.
慢性应激是精神疾病（包括抑郁症）发展的一个致病因素。它们的精神病理学机制是多方面的，包括大脑可塑性的改变。之前，我们研究了慢性社会应激对 Wistar 大鼠（海马体、HIPPO 和前额叶皮层、PFC）边缘脑结构的影响，发现了许多与一些抑郁症临床研究中描述的改变相似的特征。我们扩展了我们的研究，并通过旷场测试（OFT）和强迫游泳测试（FST）以及突触可塑性标志物神经细胞黏附分子（NCAM）和 L1 在 HIPPO 和 PFC 中的表达和多聚唾液酸化来跟踪应激动物的行为。我们还测定了肾上腺质量和血浆皮质酮（CORT）作为下丘脑-垂体-肾上腺轴活动的末端部分。我们的数据表明，应激动物回避 OFT 中的中央区域，表现出游泳减少，但 FST 中的不动时间延长。动物表现出明显的肾上腺皮质肥大，尽管血清 CORT 降低。同时，应激动物在 HIPPO 中显示 NCAM mRNA 表达增加，但在 PFC 中没有增加。HIPPO 的突触 NCAM 明显多聚唾液酸化，而皮质 PSA-NCAM 显著减少。结果表明，慢性社会隔离的 Wistar 大鼠引起焦虑样和抑郁样行为。这些改变与边缘脑的分子变化平行，包括 PFC 中 NCAM 的唾液酸化减少。结合我们以前的结果，目前的观察结果表明，慢性社会隔离模型可能被用于研究潜在的抑郁症状的分子机制。
