Temporal changes in the microglial proteome of male and female mice after a diffuse brain injury using label-free quantitative proteomics.

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These cascades may exacerbate TBI-induced tissue damage and symptoms in the months to years post-injury. However, the progression of the microglial function across time post-injury and whether this differs between biological sexes is not well understood. In this study, we examined the microglial proteome at 3-, 7-, or 28-days after a midline fluid percussion injury (mFPI) in male and female mice using label-free quantitative proteomics. Data are available via ProteomeXchange with identifier PXD033628. We identified a reduction in microglial proteins involved with clearance of neuronal debris via phagocytosis at 3- and 7-days post-injury. At 28 days post-injury, pro-inflammatory proteins were decreased and anti-inflammatory proteins were increased in microglia. These results indicate a reduction in microglial clearance of neuronal debris in the days post-injury with a shift to anti-inflammatory function by 28 days following TBI. The changes in the microglial proteome that occurred across time post-injury did not differ between biological sexes. However, we did identify an increase in microglial proteins related to pro-inflammation and phagocytosis as well as insulin and estrogen signaling in males compared with female mice that occurred with or without a brain injury. Although the microglial response was similar between males and females up to 28 days following TBI, biological sex differences in the microglial proteome, regardless of TBI, has implications for the efficacy of treatment strategies targeting the microglial response post-injury.", "claims": [{"id": "claim-method", "statement": "Univariate linear regression was used to estimate the association between explanatory variables time post‐injury (in days), biological sex, and the score for each component. All regression models were adjusted to account for batch variation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36468604", "locator": "sections[10] \"Data filtering and statistical analysis\" paragraph 3", "quote": "Univariate linear regression was used to estimate the association between explanatory variables time post‐injury (in days), biological sex, and the score for each component. All regression models were adjusted to account for batch variation."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data sharing is not applicable to this article as no new data were created or analyzed in this study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36468604", "locator": "sections[25] \"DATA AVAILABILITY STATEMENT\" paragraph 2", "quote": "Data sharing is not applicable to this article as no new data were created or analyzed in this study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "These results indicate a reduction in microglial clearance of neuronal debris in the days post‐injury with a shift to anti‐inflammatory function by 28 days following TBI.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36468604", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "These results indicate a reduction in microglial clearance of neuronal debris in the days post‐injury with a shift to anti‐inflammatory function by 28 days following TBI."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "These results indicate a reduction in microglial clearance of neuronal debris in the days post‐injury with a shift to anti‐inflammatory function by 28 days following TBI.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36468604"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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