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| Status |
Public on Jul 01, 2022 |
| Title |
Prenatal immune stress blunts microglia reactivity which impairs neurocircuitry [Adult_ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Recent studies suggested that microglia, the primary brain immune cells, can affect circuit connectivity and neuronal function. Microglia infiltrate the neuroepithelium early in embryonic development and are maintained in the brain throughout adulthood. Several maternal environmental factors, such as aberrant microbiome, immune activation, and poor nutrition, can influence prenatal brain development. Nevertheless, it is unknown how changes in the prenatal environment instruct the developmental trajectory of infiltrating microglia, which in turn affect brain development and function. Here we show that after maternal immune activation (MIA) microglia from the offspring have a long-lived decrease in immune reactivity (blunting) across the developmental trajectory. The blunted immune response was concomitant with changes in the chromatin accessibility and reduced transcription factor occupancy of the open chromatin. Single-cell RNA sequencing revealed that MIA does not induce a distinct subpopulation but rather decreases the contribution to inflammatory microglia states. Prenatal replacement of MIA microglia with physiological infiltration of naïve microglia ameliorated the immune blunting and restored a decrease in presynaptic vesicle release probability onto dopamine receptor type-two medium spiny neurons, indicating that aberrantly formed microglia due to an adverse prenatal environment impacts the long-term microglia reactivity and proper striatal circuit development.
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| Overall design |
ATAC-seq of FACS-sorted microglia (Cd11b+, Cd45-low, P2ry12+) from the striatum of control and maternal immune activation mice of 8- to 10-week-old mice after saline or LPS treatment.
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| Contributor(s) |
Hayes LN, Sawa A |
| Citation(s) |
36171283 |
| |
| Submission date |
Apr 28, 2022 |
| Last update date |
Sep 30, 2022 |
| Contact name |
Lindsay N Hayes |
| E-mail(s) |
lhayes14@jhmi.edu
|
| Organization name |
Johns Hopkins University
|
| Department |
Neuroscience
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| Street address |
600 North Wolfe Street, Meyer 4-136
|
| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21287 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (23)
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| This SubSeries is part of SuperSeries: |
| GSE201817 |
Prenatal immune stress blunts microglia reactivity which impairs neurocircuitry |
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| Relations |
| BioProject |
PRJNA833102 |
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