Astroglial Cells as Gonadal Hormone Targets: Mediators of Sex Differences in Development and Adulthood
Bibliographic record
Abstract
This doctoral thesis identifies sex differences in neocortical astroglial cells over development and delineates the role of masculinizing hormones in inducing these differences.Furthermore, we identify differences in neocortical astroglia gene and protein expression patterns across the estrous cycle in adulthood.Astroglial cells have emerged as key regulators of brain health and disease, and they are involved in various aspects of neurodevelopment, including neocortical organization, synapse development and maturation, and blood-brain barrier development.Additionally, astroglia build, maintain, and regulate neuronal networks through close modulation of neurotransmission and synaptic plasticity in development and adulthood.These studies utilized an Aldh1l1-L10a-eGFP mouse line and translating ribosome affinity purification with RNA sequencing (TRAPseq) to investigate astroglial sex differences at six developmental time points and during four different phases of the mouse estrous cycle.We found two distinct astroglial phenotypes: an "early"/developmental phenotype and a "late"/mature phenotype.Male astroglia mature more rapidly, reaching the mature phenotype by postnatal day 7 (P7), than female astroglia, which reach the mature phenotype between P7-P14.We then investigated the effects of neonatal administration of estradiol in females, which resulted in changes in gene expression and rates of maturation.During adulthood, there were no significant sex differences in astroglial cell gene expression when females were observed on metestrus, when circulating levels of ovarian hormones are lowest, however, gene expression changes were observed across the phases of the estrous cycle, with the proestrus phase being most distinct from males.These findings provide insight into the role of sex differences in neocortical astroglia and suggest potential functional Index G. M. Rurak | 2023 iii implications that may lead to sex disparities in neurodevelopmental and psychiatric disorders.As astroglial cells play a crucial role in maintaining the structural and functional integrity of the brain, it is crucial to understand how gonadal hormones influence their differentiation and function.Further research is needed to fully understand the specific mechanisms that underlie the effects of gonadal hormones on astroglial cells and how these mechanisms contribute to sex differences in brain development and function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".