Effects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice,Environmental Health Perspectives

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Effects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice
Environmental Health Perspectives ( IF 10.4 ) Pub Date : 2021-5-19 , DOI: 10.1289/ehp8428
Jacob Raber _{1,

2,

3} , Ruby Perez ₁ , Eileen Ruth S Torres ₁ , Destine Krenik ₁ , Sydney Boutros ₁ , Esha Patel ₁ , Anna C Chlebowski ₄ , Estefania Ramos Torres ₄ , Zakia Perveen ₅ , Arthur Penn ₅ , Daniel B Paulsen ₆ , Michael G Bartlett ₇ , Enze Jia ₇ , Sarah Holden ₁ , Reed Hall ₁ , Jeffrey Morré ₈ , Carmen Wong _{9,

10} , Emily Ho _{9,

11} , Jaewoo Choi ₉ , Jan Frederik Stevens _{3,

9} , Alexandra Noël ₅ , Gerd Bobe _{8,

9} , Glen Kisby ₄

Affiliation

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Departments of Neurology, Psychiatry, and Radiation Medicine, Division of Neuroscience ONPRC, Oregon Health & Science University, Portland, Oregon, USA.
College of Pharmacy, Oregon State University, Corvallis, Oregon, USA.
Department of Basic Medical Sciences, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, Oregon, USA.
Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
University of Georgia, College of Pharmacy, Athens, Georgia, USA.
Mass Spectrometry Core, Oregon State University, Corvallis, Oregon, USA.
Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
Department of Animal Sciences, Oregon State University, Corvallis, Oregon, USA.
College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon, USA.

Abstract

Background:

Exposure to secondhand smoke (SHS) is a risk factor for developing sporadic forms of sporadic dementia. A human tau (htau) mouse model is available that exhibits age-dependent tau dysregulation, neurofibrillary tangles, neuronal loss, neuroinflammation, and oxidative stress starting at an early age (3–4 months) and in which tau dysregulation and neuronal loss correlate with synaptic dysfunction and cognitive decline.

Objective:

The goal of this study was to assess the effects of chronic SHS exposure (10 months’ exposure to $approximately 30 milligrams per cubic meter$ ) on behavioral and cognitive function, metabolism, and neuropathology in mice.

Methods:

Wild-type (WT) and htau female and male mice were exposed to SHS (90% side stream, 10% main stream) using the SCIREQ® inExpose™ system or air control for 168 min per day, for 312 d, 7 d per week. The exposures continued during the days of behavioral and cognitive testing. In addition to behavioral and cognitive performance and neuropathology, the lungs of mice were examined for pathology and alterations in gene expression.

Results:

Mice exposed to chronic SHS exposure showed the following genotype-dependent responses: a) lower body weights in WT, but not htau, mice; b) less spontaneous alternation in WT, but not htau, mice in the Y maze; c) faster swim speeds of WT, but not htau, mice in the water maze; d) lower activity levels of WT and htau mice in the open field; e) lower expression of brain PHF1, TTCM1, $insulin-like growth factor 1 lowercase beta$ , and HSP90 protein levels in WT male, but not female, mice; and f) more profound effects on hippocampal metabolic pathways in WT male than female mice and more profound effects in WT than htau mice.

Discussion:

The brain of WT mice, in particular WT male mice, might be especially susceptible to the effects of chronic SHS exposure. In WT males, independent pathways involving ascorbate, flavin adenine dinucleotide, or palmitoleic acid might contribute to the hippocampal injury following chronic SHS exposure. https://doi.org/10.1289/EHP8428

中文翻译：

慢性二手烟 (SHS) 暴露对野生型和人类 Tau 小鼠海马认知能力和代谢途径的影响

摘要

背景：

接触二手烟 (SHS) 是发生散发性痴呆症的危险因素。有一种人类 tau (htau) 小鼠模型，该模型从幼年（3-4 个月）开始表现出与年龄相关的 tau 失调、神经原纤维缠结、神经元丢失、神经炎症和氧化应激，其中 tau 失调和神经元丢失与突触功能障碍和认知能力下降。

客观的：

本研究的目的是评估慢性 SHS 暴露的影响（10 个月暴露于 $approximately 30 milligrams per cubic meter$ ) 对小鼠的行为和认知功能、代谢和神经病理学的影响。

方法：

使用 SCIREQ® inExpose™ 系统或空气控制将野生型 (WT) 和 htau 雌性和雄性小鼠暴露于 SHS（90% 侧流，10% 主流），每天 168 分钟，持续 312 天，每 7 天星期。在行为和认知测试期间继续暴露。除了行为和认知表现以及神经病理学外，还检查了小鼠肺部的病理学和基因表达的改变。

结果：

长期暴露于 SHS 的小鼠表现出以下基因型依赖性反应：a ) WT 小鼠体重降低，但 htau 小鼠没有；b）在Y迷宫中WT小鼠的自发交替较少，但不是htau；c）水迷宫中WT小鼠的更快游泳速度，而不是htau小鼠；d ) WT 和 htau 小鼠在野外活动水平较低；e ) 脑 PHF1、TTCM1 的低表达， $insulin-like growth factor 1 lowercase beta$ , 和 WT 雄性小鼠而非雌性小鼠中的 HSP90 蛋白水平；和˚F）在WT雄性海马的代谢途径比WT雌性小鼠，更深远的影响比htau小鼠更深远的影响。