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| Status |
Public on Jul 07, 2020 |
| Title |
Adult mouse hippocampal transcriptome changes associated with long-term behavioral and metabolic effects of gestational air pollution toxicity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Gestational exposure to air pollution increases the risk of autism spectrum disorder and cognitive impairments with unresolved molecular mechanisms. This study exposed mice throughout gestation to urban derived nanosized particulate matter (nPM). Young adult male and female offspring were studied for behavioral and metabolic changes using forced swim test, fat gain, glucose tolerance, and hippocampal transcriptome. Gestational nPM exposure caused increased depressive behaviors, decreased neurogenesis in the dentate gyrus, and increased glucose tolerance in adult male offspring. Both sexes gained fat and body weight. Gestational nPM exposure induced 29 differentially expressed genes (DEGs) in adult hippocampus related to cytokine production, IL17a signaling, and dopamine degradation in both sexes. Stratification by sex showed 2-fold more DEGs in males than females (69 vs 37), as well as male-specific enrichment of DEGs mediating serotonin signaling, endocytosis, Gai, and cAMP signaling. Gene co-expression analysis (WCGNA) identified a module of 43 genes with divergent responses to nPM between the sexes. Chronic changes in 14 DEGs (e.g., miR9-1) were associated with depressive behaviors, adiposity and glucose intolerance. These genes enriched neuroimmune pathways such as HMGB1 and TLR4. Based on cerebral cortex transcriptome data of neonates, we traced the initial nPM responses of HMGB1 pathway. In vitro, mixed glia responded to 24 h nPM with lower HMGB1 protein and increased proinflammatory cytokines. This response was ameliorated by TLR4 knockdown. In sum, we identified transcriptional changes that could underlie air pollution mediated behavioral and phenotypic changes. These identified genes merit further studies for therapeutic intervention development.
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| Overall design |
Pregnant dams were exposed to nPM during gestational period. The effects were studied in adults.
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| Contributor(s) |
Haghani A, Johnson RG, Woodward NC, Feinberg JI, Lewis K, Ladd-Acosta C, Safi N, Jaffe AE, Sioutas C, Allayee H, Campbell DB, Volk HE, Finch CE, Morgan TE |
| Citation(s) |
32636363 |
| Submission date |
Mar 31, 2020 |
| Last update date |
Jul 13, 2020 |
| Contact name |
Amin Haghani |
| E-mail(s) |
ahaghani@altoslabs.com
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| Organization name |
Altos labs
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| Lab |
Hovath lab
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| Street address |
5510 Morehouse Dr
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| City |
San Diego |
| State/province |
CA |
| ZIP/Postal code |
92121 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA622258 |
| SRA |
SRP254792 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE147842_gene_counts_adult_hipp.csv.gz |
1.1 Mb |
(ftp)(http) |
CSV |
| GSE147842_gene_map_adult_hip.csv.gz |
1.8 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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