Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA, United States.
Department of Basic Sciences, Physiology Division, Loma Linda University School of Medicine, Loma Linda, CA, United States; Department of Pediatrics, University of California Irvine, Irvine, CA, United States.
Brain Behav Immun. 2018 May;70:96-117. doi: 10.1016/j.bbi.2018.01.011. Epub 2018 Feb 8.
Post-traumatic stress disorder (PTSD) and obesity are highly prevalent in adolescents. Emerging findings from our laboratory and others are consistent with the novel hypothesis that obese individuals may be predisposed to developing PTSD. Given that aberrant fear responses are pivotal in the pathogenesis of PTSD, the objective of this study was to determine the impact of an obesogenic Western-like high-fat diet (WD) on neural substrates associated with fear.
Adolescent Lewis rats (n = 72) were fed with either the experimental WD (41.4% kcal from fat) or the control diet. The fear-potentiated startle paradigm was used to determine sustained and phasic fear responses. Diffusion tensor imaging metrics and T2 relaxation times were used to determine the structural integrity of the fear circuitry including the medial prefrontal cortex (mPFC) and the basolateral complex of the amygdala (BLA).
The rats that consumed the WD exhibited attenuated fear learning and fear extinction. These behavioral impairments were associated with oversaturation of the fear circuitry and astrogliosis. The BLA T2 relaxation times were significantly decreased in the WD rats relative to the controls. We found elevated fractional anisotropy in the mPFC of the rats that consumed the WD. We show that consumption of a WD may lead to long-lasting damage to components of the fear circuitry.
Our findings demonstrate that consumption of an obesogenic diet during adolescence has a profound impact in the maturation of the fear neurocircuitry. The implications of this research are significant as they identify potential biomarkers of risk for psychopathology in the growing obese population.
创伤后应激障碍（PTSD）和肥胖在青少年中高发。我们实验室和其他实验室的新发现与一个新假说一致，即肥胖个体可能更容易患上 PTSD。鉴于异常的恐惧反应在 PTSD 的发病机制中起关键作用，本研究的目的是确定致肥胖的西式高脂肪饮食（WD）对与恐惧相关的神经基质的影响。
给青春期 Lewis 大鼠（n=72）喂食实验性 WD（脂肪供能 41.4%）或对照饮食。使用恐惧增强性惊跳反应范式来确定持续和瞬态恐惧反应。扩散张量成像指标和 T2 弛豫时间用于确定恐惧回路的结构完整性，包括内侧前额叶皮层（mPFC）和杏仁核基底外侧复合体（BLA）。
食用 WD 的大鼠表现出恐惧学习和恐惧消退的减弱。这些行为损伤与恐惧回路的过饱和和星形胶质细胞增生有关。与对照组相比，WD 组大鼠的 BLA T2 弛豫时间显著降低。我们发现 WD 组大鼠的 mPFC 部分各向异性分数升高。我们表明，WD 的摄入可能会对恐惧回路的成分造成持久的损害。
我们的研究结果表明，青春期摄入致肥胖饮食对恐惧神经回路的成熟有深远影响。这项研究的意义重大，因为它确定了肥胖人群中潜在的心理病理学风险生物标志物。
