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神经炎症是发展出创伤后应激障碍样表型的一个易感因素。

Neuroinflammation is a susceptibility factor in developing a PTSD-like phenotype.

作者信息

Shanazz Khadijah, Nalloor Rebecca, Lucas Rudolf, Vazdarjanova Almira

机构信息

VA Research Service, Charlie Norwood VA Medical Center, Augusta, GA, United States.

Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, United States.

出版信息

Front Behav Neurosci. 2023 Mar 29;17:1112837. doi: 10.3389/fnbeh.2023.1112837. eCollection 2023.

Abstract

INTRODUCTION

Post-Traumatic Stress Disorder (PTSD) is a psychological disorder that occurs after a traumatic event in a subset of exposed individuals. This implies the existence of susceptibility factors that foster the development of PTSD. Susceptibility factors are present before trauma and can contribute to the development and maintenance of PTSD after trauma. Manipulation of susceptibility factors may decrease the probability of developing PTSD. A putative susceptibility factor is inflammation. Patients with PTSD have been documented to have a higher pro-inflammatory profile compared to non-PTSD subjects. In addition, they are more likely to develop and die from cardiovascular disease which has a strong inflammation component. It is not known, however, whether inflammation plays a role in developing PTSD or whether reducing inflammation can prevent PTSD.

METHODS

We used the Revealing Individual Susceptibility to a PTSD-like phenotype (RISP) model to behaviorally classify male rats as resilient or susceptible before trauma and tested their serum and prefrontal cortical (mPFC) levels of IL-1β, IL-6, TNFα, IL-10, IFN IFNγ, and KC/GRO to determine whether inflammation represents a putative susceptibility factor for PTSD.

RESULTS

We found elevated IL-6 levels in the mPFC, but not serum, of susceptible rats compared to resilient animals before trauma. Serum and mPFC levels were not correlated in any of the cytokines/chemokines. Rats with high anxiety-like behavior had elevated IL-6 and IL-10 mPFC levels. Acoustic startle responses were not associated with cytokine/chemokine levels.

DISCUSSION

Neuroinflammation, rather than systemic inflammation exists in susceptible male rats before trauma and is thus a putative susceptibility factor for PTSD. Thus, susceptibility appears neurogenic in its pathogenesis. The lack of differences between susceptible and resilient rats in serum cytokine/chemokine levels infers that peripheral markers will not be useful in determining susceptibility. Chronic neuroinflammation appears more broadly associated with anxiety rather than startle responses.

摘要

引言

创伤后应激障碍(PTSD)是一种心理障碍,在一部分经历创伤事件的个体中出现。这意味着存在促进PTSD发展的易感性因素。易感性因素在创伤前就已存在,并可在创伤后促使PTSD的发展和维持。对易感性因素的调控可能会降低患PTSD的概率。一种假定的易感性因素是炎症。与非PTSD受试者相比,PTSD患者的促炎特征更高。此外,他们更有可能患心血管疾病并死于心血管疾病,而心血管疾病有很强的炎症成分。然而,尚不清楚炎症是否在PTSD的发展中起作用,或者减轻炎症是否可以预防PTSD。

方法

我们使用揭示个体对PTSD样表型的易感性(RISP)模型,在创伤前将雄性大鼠行为分类为有恢复力或易感性,并检测它们血清和前额叶皮质(mPFC)中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNFα)、白细胞介素-10(IL-10)、干扰素γ(IFNγ)和KC/GRO的水平,以确定炎症是否代表PTSD的一种假定易感性因素。

结果

我们发现,与创伤前有恢复力的动物相比,易感性大鼠的mPFC中IL-6水平升高,但血清中未升高。在任何细胞因子/趋化因子中,血清和mPFC水平均无相关性。具有高焦虑样行为的大鼠mPFC中IL-6和IL-10水平升高。听觉惊吓反应与细胞因子/趋化因子水平无关。

讨论

在创伤前,易感性雄性大鼠中存在神经炎症而非全身炎症,因此是PTSD的一种假定易感性因素。因此,易感性在其发病机制中似乎是神经源性的。易感性大鼠和有恢复力大鼠在血清细胞因子/趋化因子水平上没有差异,这表明外周标志物在确定易感性方面没有用处。慢性神经炎症似乎更广泛地与焦虑相关,而不是与惊吓反应相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff14/10090279/ec4f9d681a8b/fnbeh-17-1112837-g001.jpg

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