光遗传刺激基底前脑胆碱能神经元可预防普利斯坦诱导狼疮小鼠的神经炎症和神经精神症状。

IF 4.7 2区 心理学 Q1 BEHAVIORAL SCIENCES
Yang Yun, Xuejiao Wang, Jingyi Xu, Jingyu Chen, Xueru Wang, Pingting Yang, Ling Qin
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引用次数: 0

摘要

背景:神经炎症已被确定为神经精神系统性红斑狼疮(NPSLE)的主要致病因素之一。然而,临床上没有专门的治疗方法来减轻NPSLE的神经炎症。已经提出刺激基底前脑(BF)胆碱能神经元可能在几种炎症性疾病中提供有效的抗炎作用,但其在NPSLE中的潜在作用仍未被探索。本研究旨在探讨刺激BF胆碱能神经元是否及如何对NPSLE有保护作用。结果:光遗传刺激BF胆碱能神经元可显著改善普利坦诱导狼疮(PIL)小鼠的嗅觉功能障碍和焦虑和抑郁样表型。粘附分子(p -选择素和血管细胞粘附分子-1 (VCAM-1))的表达增加,白细胞募集,血脑屏障(BBB)渗漏明显减少。值得注意的是,脑组织病理学改变,包括促炎细胞因子(TNF-α, IL-6和IL-1β)水平升高,脉膜丛和侧脑室壁IgG沉积以及皮质和海马神经元脂褐素积累也明显减弱。此外,我们还证实了BF胆碱能突起与脑血管的共定位,以及α7-烟碱乙酰胆碱受体(α7nAChR)在脑血管上的表达。结论:我们的数据表明,刺激BF胆碱能神经元可能通过其对脑血管的胆碱能抗炎作用而发挥神经保护作用。因此,这可能是NPSLE的一个有希望的预防目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

Background: Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE.

Results: Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels.

Conclusion: Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.

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来源期刊
Behavioral and Brain Functions
Behavioral and Brain Functions 医学-行为科学
CiteScore
5.90
自引率
0.00%
发文量
11
审稿时长
6-12 weeks
期刊介绍: A well-established journal in the field of behavioral and cognitive neuroscience, Behavioral and Brain Functions welcomes manuscripts which provide insight into the neurobiological mechanisms underlying behavior and brain function, or dysfunction. The journal gives priority to manuscripts that combine both neurobiology and behavior in a non-clinical manner.
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