Molteni Raffaella, Calabrese Francesca, Bedogni Francesco, Tongiorgi Enrico, Fumagalli Fabio, Racagni Giorgio, Riva Marco Andrea
Center of Neuropharmacology, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases (CEND), University of Milan, Milan, Italy.
Int J Neuropsychopharmacol. 2006 Jun;9(3):307-17. doi: 10.1017/S1461145705005766. Epub 2005 Jul 22.
During the last few years several studies have highlighted the possibility that major depression can be characterized by a general reduction in brain plasticity and an increased vulnerability under challenging situations. Such dysfunction may be the consequence of reduced expression and function of proteins important for neuroplasticity such as brain-derived neurotrophic factor (BDNF). On this basis, by using a sensitive non-radioactive in-situ hybridization, we evaluated the effects of a chronic treatment with fluoxetine on BDNF expression within rat dopaminergic regions. In fact, besides the well-established role of the hippocampus, increasing evidence indicates that other brain regions may be involved in the pathophysiology of depression and consequently be relevant for the therapeutic action of antidepressant drugs. Our results indicate that 3 wk of fluoxetine administration up-regulates BDNF mRNA levels selectively within structures belonging to the meso-cortico-limbic pathway. The expression of the neurotrophin is significantly increased in the ventral tegmental area, prefrontal cortex, and shell region of the nucleus accumbens, whereas no changes were detected in the substantia nigra and striatum. Moreover, in agreement with previous studies, fluoxetine increased BDNF mRNA levels in the hippocampus, an effect that was limited to the cell bodies without any change in its dendritic targeting. These data show that chronic treatment with fluoxetine increases BDNF gene expression not only in limbic areas but also in dopaminergic regions, suggesting that such an effect may contribute to improve the function of the dopaminergic system in depressed subjects.
在过去几年中，多项研究强调了重度抑郁症可能具有大脑可塑性普遍降低以及在挑战性情境下易损性增加的特征。这种功能障碍可能是对神经可塑性至关重要的蛋白质（如脑源性神经营养因子，BDNF）表达和功能降低的结果。在此基础上，我们使用灵敏的非放射性原位杂交技术，评估了氟西汀长期治疗对大鼠多巴胺能区域内BDNF表达的影响。事实上，除了海马体已明确的作用外，越来越多的证据表明其他脑区可能参与抑郁症的病理生理学过程，因此与抗抑郁药物的治疗作用相关。我们的结果表明，给予氟西汀3周可选择性地上调中脑 - 皮质 - 边缘通路所属结构内的BDNF mRNA水平。神经营养因子的表达在腹侧被盖区、前额叶皮质和伏隔核壳区显著增加，而在黑质和纹状体中未检测到变化。此外，与先前的研究一致，氟西汀增加了海马体中的BDNF mRNA水平，这种效应仅限于细胞体，其树突靶向没有任何变化。这些数据表明，氟西汀长期治疗不仅增加了边缘区域的BDNF基因表达，还增加了多巴胺能区域的表达，表明这种效应可能有助于改善抑郁症患者多巴胺能系统的功能。
