神经炎症导致海马结构中多巴胺能神经元的功能不合理，被认为在抑郁症的病理生理学中扮演重要角色。本研究的目的是利用脂多糖(LPS)、γ干扰素(IFNγ)、β-淀粉样蛋白₁₋₄₂或肿瘤坏死因子-α在简单的海马结构多巴胺能神经元大脑切片模型中诱导神经炎症，以探索多巴胺能神经元的细胞存活和色氨酸降解酶吲哚胺 2，3-二氧化酶(IDO)的表达。体内注射促炎症刺激可以减少多巴胺能神经元海马结构切片的存活并增加IDO的表达。IFNγ最有效地诱导IDO的表达，它与神经元共定位，包括多巴胺能神经元，但不与微胶质细胞或星形胶质细胞共定位。IFNγ未诱导切片中PI阳性染色，但增加了IDO阳性细胞的平均核大小。当切片从炎症中退出时，炎症诱导的下降并未返回到控制水平，这指向神经退行性疾病。生长因子BDNF或GDNF无法抵消炎症诱导的多巴胺能神经元减少，除了LPS诱导的神经元退化。炎症诱导的效应未被NMDA受体拮抗剂MK-801阻断。进一步证明，LPS而不是IFNγ增加了炎症标记和微胶质细胞活性。总而言之，我们的数据表明，一系列炎症刺激会减少多巴胺能神经元在中的细胞存活，并上调IDO的表达。数据表明IDO不会导致多巴胺能神经元下降，但可能作为神经退行性的标志物。神经炎症可能导致抑郁症的发展。版权所有©2011 IBRO。由Elsevier Ltd.出版。保留所有权利。

Neuroinflammation results in dysregulation of serotonergic neurons in the dorsal raphe nucleus (doR) and is considered to play an important role in the pathophysiology of depression. The aim of the present study was to induce neuroinflammation in a simple doR brain slice model using lipopolysaccharide (LPS), interferon-gamma (IFNγ), beta-amyloid₁₋₄₂ or tumor necrosis factor-alpha and to explore the survival of serotonergic neurons and the expression of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO). Administration of pro-inflammatory stimuli reduced survival of serotonergic neurons in doR slices and increased IDO expression. IFNγ most potently induced IDO expression, which co-localized with neurons, including serotonergic neurons, but not with microglia or astrocytes. IFNγ did not induce PI-positive staining in slices, but increased the average nuclei size of IDO-positive cells. The inflammation-induced decline did not return to control levels, when slices were withdrawn from inflammation, pointing to neurodegeneration. The growth factors BDNF or GDNF did not counteract the inflammation-induced decrease in serotonergic neurons, except for LPS-induced neuronal decline. The inflammation-induced effect was not blocked by the NMDA-receptor antagonist MK-801. Further LPS, but not IFNγ increased inflammatory markers and microglia activity. In conclusion, our data show that a range of inflammatory stimuli decline serotonergic neurons in doR slices and upregulate IDO expression. The data suggest that IDO does not contribute to serotonergic decline, but may serve as a marker of neurodegeneration. Neuroinflammation may contribute to the development of depression.Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.