Katarzyna Głombik, Magdalena Kukla-Bartoszek, Katarzyna Curzytek, Agnieszka Basta-Kaim, Bogusława Budziszewska
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引用次数: 0
摘要
背景:妊娠期间母体糖皮质激素水平升高会影响发育中的胎儿,永久性地改变其一生的大脑结构和功能。众所周知,这些激素的过度作用会导致包括抑郁症在内的精神疾病:研究在大鼠抑郁症模型中进行,该模型基于在妊娠晚期产前给予地塞米松(DEX)(0.1 毫克/千克,第 14-21 天)。我们通过行为和生化测试,评估了产前地塞米松治疗对成年雄性大鼠大脑认知和生物能信号通路、额叶皮层和海马以及成年后对应激反应的影响:结果:我们发现产前用 DEX 治疗的大鼠存在认知缺陷。在分子水平上,我们观察到这些动物额叶皮层的奥曲肽 A 和奥曲肽 B 水平下降,AMPK-SIRT1-PGC1α 转导通路下调。在海马中,奥曲肽 B 的表达量减少,MR/GR 的比率也发生了变化。此外,有报告称,产前DEX处理会导致两种大脑结构中的HDAC5水平升高,海马中的MeCP2水平降低:我们的研究表明,产前DEX治疗与认知功能障碍和导致额叶皮层代谢变化的各种蛋白质的改变有关,而海马的适应机制被激活。这些结果表明,不同的病理生理代谢过程可能与抑郁症的发展有关,这可能有助于寻找新的疗法。
Contribution of changes in the orexin system and energy sensors in the brain in depressive disorder - a study in an animal model.
Background: Maternal elevated glucocorticoid levels during pregnancy can affect the developing fetus, permanently altering the structure and function of its brain throughout life. Excessive action of these hormones is known to contribute to psychiatric disorders, including depression.
Materials: The study was performed in a rat model of depression based on prenatal administration of dexamethasone (DEX) in late pregnancy (0.1 mg/kg, days 14-21). We evaluated the effects of prenatal DEX treatment on the cognition and bioenergetic signaling pathways in the brain of adult male rats, in the frontal cortex and hippocampus, and in response to stress in adulthood, using behavioral and biochemical test batteries.
Results: We revealed cognitive deficits in rats prenatally treated with DEX. At the molecular level, a decrease in the orexin A and orexin B levels and downregulation of the AMPK-SIRT1-PGC1α transduction pathway in the frontal cortex of these animals were observed. In the hippocampus, a decreased expression of orexin B was found and changes in the MR/GR ratio were demonstrated. Furthermore, an increase in HDAC5 level triggered by the prenatal DEX treatment in both brain structures and a decrease in MeCP2 level in the hippocampus were reported.
Conclusions: Our study demonstrated that prenatal DEX treatment is associated with cognitive dysfunction and alterations in various proteins leading to metabolic changes in the frontal cortex, while in the hippocampus adaptation mechanisms were activated. The presented results imply that different pathophysiological metabolic processes may be involved in depression development, which may be useful in the search for novel therapies.
期刊介绍:
Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures.
Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology.
Studies of plant extracts are not suitable for Pharmacological Reports.