Basta-Kaim A, Szczesny E, Glombik K, Slusarczyk J, Trojan E, Tomaszewski K A, Budziszewska B, Kubera M, Lason W
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St, 31-343 Krakow, Poland.
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St, 31-343 Krakow, Poland.
Neuroscience. 2014 Aug 22;274:59-68. doi: 10.1016/j.neuroscience.2014.05.010. Epub 2014 May 21.
Depression is a mental disorder of still unknown origin. Currently, much attention is paid to the potential influence of disturbances in the functioning of neurotrophic factors on the onset of this disease. Insulin-like growth factor 1 (IGF-1) is one of the most important growth agents affecting processes that are crucial for brain development. To date, there are no data showing the impact of prenatal stress on the family of six IGF binding proteins (IGFBP 1-6) that regulate IGF-1 bioactivity. The goal of this study was to investigate whether the decreased expression of IGF-1 in the frontal cortex (FCx) and hippocampus (Hp) of adult male rats following a prenatal stress procedure is related to changes in the IGFBP family. Our results show that rats exposed prenatally to stressful stimuli displayed depression-like behavior based on sucrose preference and elevated plus maze tests. In both cases, in the adult rat brain structures that were examined after the prenatal stress procedure, the IGF-1 protein level was reduced. Moreover, we observed changes of varying degrees in the levels of IGFBPs in stressed animals. A decrease in IGFBP-2 and IGFBP-3 accompanied by an increase in the IGFBP-4 concentration in the Hp and the FCx was detected. There were no differences in IGFBP-1 and IGFBP-6 brain levels between the stressed and control animals, whereas IGFBP-5 concentration was decreased in the Hp of prenatally stressed animals. This study demonstrated that stress during pregnancy may lead not only to behavioral disturbances but also to a decrease in IGF-1 level and the dysregulation of the IGF-1 binding protein network in adult rat offspring.
抑郁症是一种病因尚不明确的精神障碍。目前,人们十分关注神经营养因子功能紊乱对该疾病发病的潜在影响。胰岛素样生长因子1(IGF-1)是影响大脑发育关键过程的最重要生长因子之一。迄今为止,尚无数据表明产前应激对调节IGF-1生物活性的六种IGF结合蛋白(IGFBP 1-6)家族有何影响。本研究的目的是调查成年雄性大鼠在经历产前应激后,额叶皮质(FCx)和海马体(Hp)中IGF-1表达降低是否与IGFBP家族的变化有关。我们的结果表明,根据蔗糖偏好和高架十字迷宫试验,产前暴露于应激刺激的大鼠表现出类似抑郁的行为。在这两种情况下,在产前应激程序后检查的成年大鼠脑结构中,IGF-1蛋白水平均降低。此外,我们观察到应激动物体内IGFBPs水平有不同程度的变化。在Hp和FCx中检测到IGFBP-2和IGFBP-3减少,同时IGFBP-4浓度增加。应激动物和对照动物的脑内IGFBP-1和IGFBP-6水平没有差异,而产前应激动物的Hp中IGFBP-5浓度降低。本研究表明,孕期应激不仅可能导致行为障碍,还可能导致成年大鼠后代的IGF-1水平降低和IGF-1结合蛋白网络失调。