抑郁症是一种严重的情绪障碍，其特征是单胺缺乏、氧化应激、神经炎症和细胞死亡。烟酸（维生素B3或烟酸，NA）是中枢神经系统中神经元发育和存活的主要调节因子，在几个实验模型中具有神经保护作用。本研究旨在调查NA对脂多糖（LPS）诱导的抑郁小鼠模型的影响，探索其调节sirtuin1/多聚(ADP核糖)聚合酶-1（PARP-1）/NLRP3信号的能力。小鼠每隔一天注射LPS（500 µg/kg, i.p），单独或同时口服NA（40 mg/kg/day）或唑达洛平（10 mg/kg/day）持续14天。NA的给药导致动物在强制性游泳实验中的绝望感明显减少，表现为行动时间的减少。此外，NA诱导了单胺的增加，同时激活了sirtuin1，随后下调了海马中的PARP-1。此外，它减少了核因子κB（NF-κB）的水平，抑制了NLRP3炎症小体，进而降低了升级酶1、白介素-1β和肿瘤坏死因子-α的水平，从而缓解了LPS诱导的神经炎症。NA还降低了肿瘤抑制蛋白（p53）的水平，并提高了脑源性神经营养因子的水平。NA的给药逆转了LPS引起的神经细胞生存下降，组织病理学切片中显示出明显增加的完整细胞数量。因此，NA被认为是通过靶向SIRT1/PARP-1途径进行抑郁症管理的有希望的候选药物。版权所有 © 2023 Elsevier B.V.。保留所有权利。

Depression is a serious mood disorder characterized by monoamines deficiency, oxidative stress, neuroinflammation, and cell death. Niacin (vitamin B3 or nicotinic acid, NA), a chief mediator of neuronal development and survival in the central nervous system, exerts neuroprotective effects in several experimental models.This study aimed to investigate the effect of NA in lipopolysaccharide (LPS) mouse model of depression exploring its ability to regulate sirtuin1/poly (ADP-ribose) polymerase-1 (PARP-1)/nod-likereceptor protein 3 (NLRP3) signaling.Mice were injected with LPS (500 µg/kg, i.p) every other day alone or concurrently with oral doses of either NA (40 mg/kg/day) or escitalopram (10 mg/kg/day) for 14 days.Administration of NA resulted in significant attenuation of animals' despair reflected by decreased immobility time in forced swimming test. Moreover, NA induced monoamines upsurge in addition to sirtuin1 activation with subsequent down regulation of PARP-1 in the hippocampus. Further, it diminished nuclear factor-κB (NF-κB) levels and inhibited NLRP3 inflammasome with consequent reduction of caspase-1, interleukin-1β and tumor necrosis factor-α levels, thus mitigating LPS-induced neuroinflammation. NA also reduced tumor suppressor protein (p53) while elevating brain-derived neurotrophic factor levels. LPS-induced decline in neuronal survival was reversed by NA administration with an obvious increase in the number of intact cells recorded in the histopathological micrographs.Accordingly, NA is deemed as a prosperous candidate for depression management via targeting SIRT1/PARP-1 pathway.Copyright © 2023 Elsevier B.V. All rights reserved.