TitleEffects of Chronic Secondhand Smoke (SHS) Exposure on Cognitive Performance and Metabolic Pathways in the Hippocampus of Wild-Type and Human Tau Mice.
Publication TypeJournal Article
Year of Publication2021
AuthorsRaber, J, Perez, R, Torres, ERuth S, Krenik, D, Boutros, S, Patel, E, Chlebowski, AC, Torres, ERamos, Perveen, Z, Penn, A, Paulsen, DB, Bartlett, MG, Jia, E, Holden, S, Hall, R, Morré, J, Wong, CP, Ho, E, Choi, J, Stevens, JF, Noël, A, Bobe, G, Kisby, G
JournalEnviron Health Perspect
Date Published2021 05
KeywordsAnimals, Cognition, Environmental Exposure, Female, Hippocampus, Humans, Male, Metabolic Networks and Pathways, Mice, tau Proteins, Tauopathies, Tobacco Smoke Pollution

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.

Alternate JournalEnviron Health Perspect
PubMed ID34009016
PubMed Central IDPMC8132614
Grant ListF31 AG067629 / AG / NIA NIH HHS / United States
P30 ES030287 / ES / NIEHS NIH HHS / United States
R21 ES027943 / ES / NIEHS NIH HHS / United States
T32 AG055378 / AG / NIA NIH HHS / United States