@article {329, title = {Genetic background influences the effect of thirdhand smoke exposure on anxiety and memory in Collaborative Cross mice.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 06 24}, pages = {13285}, abstract = {

Growing evidence indicates that thirdhand smoke (THS) exposure induces many adverse health effects. However, it is unclear how THS exposure affects behavior and how host genetic background modulates phenotypic changes. Here we used the Collaborative Cross (CC) mouse population-based model to assess behavioral alterations immediately after THS exposure from 4 to 9\ weeks of age. We first measured anxiety-like behavior in six strains using light/dark box combined with a custom multivariate mouse tracking system. We developed an anxiety risk scoring system based on anxiety-related traits and then evaluated the THS impact on them. THS exposure significantly decreased anxiety risk in CC019 (P = 0.002) and CC051 (P = 0.009), but increased anxiety risk in CC036 (P \< 0.001), while the other three strains did not show significant changes in anxiety-related traits. Such differences were driven by female mice for the six measures of anxiety-like behavior. Memory potential was measured in the same cohort of mice using the passive avoidance assay. Both THS-exposed male and female CC019 mice displayed significant memory loss compared to controls while no significant changes were found in the other five strains. This study provides strong evidence that THS exposure leads to strain-dependent changes in anxiety-like behavior and memory, suggesting that host genetic variations play a critical role in individual susceptibility to THS-induced effects.

}, keywords = {Animals, Anxiety, Collaborative Cross Mice, Female, Humans, Male, Memory, Risk Factors, Tobacco Smoke Pollution}, issn = {2045-2322}, doi = {10.1038/s41598-021-92702-1}, author = {He, Li and Wang, Pin and Schick, Suzyann F and Huang, Abel and Jacob, Peyton and Yang, Xu and Xia, Yankai and Snijders, Antoine M and Mao, Jian-Hua and Chang, Hang and Hang, Bo} } @article {324, title = {Gut microbiome partially mediates and coordinates the effects of genetics on anxiety-like behavior in Collaborative Cross mice.}, journal = {Sci Rep}, volume = {11}, year = {2021}, month = {2021 01 11}, pages = {270}, abstract = {

Growing evidence suggests that the gut microbiome (GM) plays a critical role in health and disease. However, the contribution of GM to psychiatric disorders, especially anxiety, remains unclear. We used the Collaborative Cross (CC) mouse population-based model to identify anxiety associated host genetic and GM factors. Anxiety-like behavior of 445 mice across 30 CC strains was measured using the light/dark box assay and documented by video. A custom tracking system was developed to quantify seven anxiety-related phenotypes based on video. Mice were assigned to a low or high anxiety group by consensus clustering using seven anxiety-related phenotypes. Genome-wide association analysis (GWAS) identified 141 genes (264 SNPs) significantly enriched for anxiety and depression related functions. In the same CC cohort, we measured GM composition and identified five families that differ between high and low anxiety mice. Anxiety level was predicted with 79\% accuracy and an AUC of 0.81. Mediation analyses revealed that the genetic contribution to anxiety was partially mediated by the GM.\ Our findings indicate that GM partially mediates and coordinates the effects of genetics on anxiety.

}, keywords = {Animals, Anxiety, Behavior, Animal, Collaborative Cross Mice, Gastrointestinal Microbiome, Mice}, issn = {2045-2322}, doi = {10.1038/s41598-020-79538-x}, author = {Jin, X and Zhang, Y and Celniker, S E and Xia, Y and Mao, J-H and Snijders, A M and Chang, Hang} } @article {309, title = {Genetic and metabolic links between the murine microbiome and memory.}, journal = {Microbiome}, volume = {8}, year = {2020}, month = {2020 04 17}, pages = {53}, abstract = {

BACKGROUND: Recent evidence has linked the gut microbiome to host behavior via the gut-brain axis [1-3]; however, the underlying mechanisms remain unexplored. Here, we determined the links between host genetics, the gut microbiome and memory using the genetically defined Collaborative Cross (CC) mouse cohort, complemented with microbiome and metabolomic analyses in conventional and germ-free (GF) mice.

RESULTS: A genome-wide association analysis (GWAS) identified 715 of 76,080 single-nucleotide polymorphisms (SNPs) that were significantly associated with short-term memory using the passive avoidance model. The identified SNPs were enriched in genes known to be involved in learning and memory functions. By 16S rRNA gene sequencing of the gut microbial community in the same CC cohort, we identified specific microorganisms that were significantly correlated with longer latencies in our retention test, including a positive correlation with Lactobacillus. Inoculation of GF mice with individual species of Lactobacillus (L. reuteri F275, L. plantarum BDGP2 or L. brevis BDGP6) resulted in significantly improved memory compared to uninoculated or E. coli DH10B inoculated controls. Untargeted metabolomics analysis revealed significantly higher levels of several metabolites, including lactate, in the stools of Lactobacillus-colonized mice, when compared to GF control mice. Moreover, we demonstrate that dietary lactate treatment alone boosted memory in conventional mice. Mechanistically, we show that both inoculation with Lactobacillus or lactate treatment significantly increased the levels of the neurotransmitter, gamma-aminobutyric acid (GABA), in the hippocampus of the mice.

CONCLUSION: Together, this study provides new evidence for a link between Lactobacillus and memory and our results open possible new avenues for treating memory impairment disorders using specific gut microbial inoculants and/or metabolites. Video Abstract.

}, issn = {2049-2618}, doi = {10.1186/s40168-020-00817-w}, author = {Mao, Jian-Hua and Kim, Young-Mo and Zhou, Yan-Xia and Hu, Dehong and Zhong, Chenhan and Hang Chang and Brislawn, Colin J and Fansler, Sarah and Langley, Sasha and Wang, Yunshan and Peisl, B Y Loulou and Celniker, Susan E and Threadgill, David W and Wilmes, Paul and Orr, Galya and Metz, Thomas O and Jansson, Janet K and Snijders, Antoine M} } @article {41, title = {Graphical methods for quantifying macromolecules through bright field imaging}, journal = {Bioinformatics}, volume = {25}, year = {2009}, pages = {1070{\textendash}1075}, doi = {10.1093/bioinformatics/btn426}, url = {http://dx.doi.org/10.1093/bioinformatics/btn426}, author = {Hang Chang and Rosa Anna DeFilippis and Thea D. Tlsty and Bahram Parvin} }