Effects of chronic secondhand smoke (Shs) exposure on cognitive performance and metabolic pathways in the hippocampus of wild-type and human tau mice

Jacob Raber, Ruby Perez, Eileen Ruth S. Torres, Destine Krenik, Sydney Boutros, Esha Patel, Anna C. Chlebowski, Estefania Ramos Torres, Zakia Perveen, Arthur Penn, Daniel B. Paulsen, Michael G. Bartlett, Enze Jia, Sarah Holden, Reed Hall, Jeffrey Morré, Carmen Wong, Emily Ho, Jaewoo Choi, Jan Frederik StevensAlexandra Noël, Gerd Bobe, Glen Kisby

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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 ∼ 30 mg/m3 ) 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, IGF1β, 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.

Original languageEnglish (US)
Article number057009
JournalEnvironmental health perspectives
Issue number5
StatePublished - 2021

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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