不同类别的抗抑郁药会导致处于抑郁炎症模型中的小鼠产生不同的行为和大脑促炎及抗炎变化。
Antidepressants of different classes cause distinct behavioral and brain pro- and anti-inflammatory changes in mice submitted to an inflammatory model of depression.
机构信息
Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.
Department of Microbiology and Immunology, and Department of Medicine, Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina, USA.
出版信息
J Affect Disord. 2020 May 1;268:188-200. doi: 10.1016/j.jad.2020.03.022. Epub 2020 Mar 6.
BACKGROUND
Depressed patients present increased plasma levels of lipopolysaccharide (LPS) and neuroinflammatory alterations. Here, we determined the neuroimmune effects of different classes of ADs by using the LPS inflammatory model of depression.
METHODS
Male rats received amitriptyline (AMI) a tricyclic, S-citalopram (ESC) a selective serotonin reuptake inhibitor, tranylcypromine (TCP) a monoamine oxidase inhibitor, vortioxetine (VORT) a multimodal AD or saline for ten days. One-hour after the last AD administration, rats were exposed to LPS 0.83 mg/kg or saline and 24 h later were tested for depressive-like behavior. Plasma corticosterone, brain levels of nitrite, pro- and anti-inflammatory cytokines, phospho-cAMP Response Element-Binding Protein (CREB) and nuclear factor (NF)-kB p 65 were determined.
RESULTS
LPS induced despair-like, impaired motivation/self-care behavior and caused anhedonia. All ADs prevented LPS-induced despair-like behavior, but only VORT rescued impaired self-care behavior. All ADs prevented LPS-induced increase in brain pro-inflammatory cytokines [interleukin (IL)-1β and IL-6] and T-helper 1 cytokines [tumor necrosis factor (TNF)-α and interferon-γ]. VORT increased striatal and hypothalamic IL-4 levels. All ADs prevented LPS-induced neuroendocrine alterations represented by increased levels of hypothalamic nitrite and plasma corticosterone response. VORT and ESC prevented LPS-induced increase in NF-kBp65 hippocampal expression, while ESC, TCP and VORT, but not IMI, prevented the alterations in phospho-CREB expression.
LIMITATIONS
LPS model helps to understand depression in a subset of depressed patients with immune activation. The levels of neurotransmitters were not determined.
CONCLUSION
This study provides new evidence for the immunomodulatory effects of ADs, and shows a possible superior anti-inflammatory profile of TCP and VORT.
背景
抑郁患者的血浆脂多糖（LPS）水平升高，神经炎症发生改变。在这里，我们通过使用 LPS 诱导的抑郁模型来确定不同类别的抗抑郁药的神经免疫效应。
方法
雄性大鼠连续十天接受阿米替林（AMI）、西酞普兰（ESC）、曲马多（TCP）、文拉法辛（VORT）或生理盐水治疗。最后一次 AD 给药后 1 小时，大鼠暴露于 LPS（0.83mg/kg）或生理盐水，24 小时后进行抑郁样行为测试。测定血浆皮质酮、脑内亚硝酸盐、促炎和抗炎细胞因子、磷酸化 cAMP 反应元件结合蛋白（CREB）和核因子（NF）-kB p65 的水平。
结果
LPS 诱导出绝望、动机受损/自我护理行为和快感缺失。所有 AD 均能预防 LPS 诱导的绝望样行为，但只有 VORT 能挽救受损的自我护理行为。所有 AD 均能预防 LPS 诱导的脑内促炎细胞因子（IL-1β和 IL-6）和 T 辅助 1 细胞因子（TNF-α和干扰素-γ）增加。VORT 增加纹状体和下丘脑的 IL-4 水平。所有 AD 均能预防 LPS 诱导的神经内分泌改变，表现为下丘脑亚硝酸盐和血浆皮质酮反应的增加。VORT 和 ESC 可预防 LPS 诱导的 NF-kBp65 海马表达增加，而 ESC、TCP 和 VORT（而非 IMI）可预防 CREB 表达的改变。
局限性
LPS 模型有助于了解具有免疫激活的抑郁患者的亚组中的抑郁。未测定神经递质的水平。
结论
本研究为 AD 的免疫调节作用提供了新的证据，并显示 TCP 和 VORT 可能具有更好的抗炎作用。
Zotero 插件