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

Authors

Jacob Raber, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Ruby Perez, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Eileen Ruth Torres, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Destine Krenik, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Sydney Boutros, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Esha Patel, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Anna C. Chlebowski, Department of Basic Medical Sciences, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, Oregon, USA.
Estefania Ramos Torres, Department of Basic Medical Sciences, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, Oregon, USA.
Zakia Perveen, Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Arthur Penn, Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Daniel B. Paulsen, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Michael G. Bartlett, University of Georgia, College of Pharmacy, Athens, Georgia, USA.
Enze Jia, University of Georgia, College of Pharmacy, Athens, Georgia, USA.
Sarah Holden, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Reed Hall, Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA.
Jeffrey Morré, Mass Spectrometry Core, Oregon State University, Corvallis, Oregon, USA.
Carmen Wong, Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
Emily Ho, Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
Jaewoo Choi, Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
Jan Frederik Stevens, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA.
Alexandra Noël, Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA.
Gerd Bobe, Mass Spectrometry Core, Oregon State University, Corvallis, Oregon, USA.
Glen Kisby, Department of Basic Medical Sciences, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific Northwest, Lebanon, Oregon, USA.

Document Type

Article

Publication Date

5-1-2021

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 ) 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: ) lower body weights in WT, but not htau, mice; ) less spontaneous alternation in WT, but not htau, mice in the Y maze; ) faster swim speeds of WT, but not htau, mice in the water maze; ) lower activity levels of WT and htau mice in the open field; ) lower expression of brain PHF1, TTCM1, , and HSP90 protein levels in WT male, but not female, mice; and ) 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.

Publication Source (Journal or Book title)

Environmental health perspectives

First Page

57009

Recommended Citation

Raber, J., Perez, R., Torres, E. R., Krenik, D., Boutros, S., Patel, E., Chlebowski, A. C., Torres, E. R., Perveen, Z., Penn, A., Paulsen, D. B., Bartlett, M. G., Jia, E., Holden, S., Hall, R., Morré, J., Wong, C., Ho, E., Choi, J., Stevens, J. F., Noël, A., Bobe, G., & Kisby, G. (2021). 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, 129 (5), 57009. https://doi.org/10.1289/EHP8428