SUN-467 Vitamin B6 and N-Acetylcysteine Protect Hypothalamic Neurons from Bisphenol A-Mediated Induction of Neuropeptide Y Gene Expression
Bibliographic record
Abstract
Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical with estrogenic properties, disrupts reproductive function, but is also considered an obesogen. Potential targets of BPA are the neuropeptide Y (NPY) neurons of the hypothalamus as specific sub-populations act to increase food intake, while others regulate the hypothalamic-pituitary-gonadal axis, thereby coordinating reproduction. We previously found that BPA upregulated Npy mRNA expression in four hypothalamic cell lines (mHypoA-59, mHypoA-2/12, mHypoE-41, mHypoE-42) across 24 hours, potentially contributing to the obesogenic effect of BPA, whereas it decreased Npy expression in two cell lines (mHypoE-46, mHypoE-44). These differential responses may reflect cell-specific differences that exist within hypothalamic NPY neurons functioning to coordinate either energy balance or reproduction. We also found that BPA increased markers of neuroinflammation (Il6, Tnfα, Il10) and inducible nitric oxide synthase (iNos) in mHypoA-59 and mHypoE-41 cells. Therefore, we hypothesized that BPA alters Npy expression through induction of neuroinflammation or oxidative stress. Inhibition of the NFkB inflammatory pathway (PS1145) or iNOS (L-NAME or TRIM) did not abrogate the BPA-mediated Npy induction, demonstrating that inflammation and iNOS do not appear to upregulate Npy. Interestingly, treatment of the mHypoA-59 cells with BPA in an antioxidant-rich media, neurobasal A (NBA), mitigated the BPA-induced increase in Npy. A comparison of NBA and Dulbecco’s modified Eagle’s medium revealed three major advantages to NBA: the presence of vitamin B12 and bio-available forms of vitamin B6 and L-cysteine. Treatment with BPA in the presence of N-acetylcysteine or vitamin B6, but not vitamin B12, demonstrated an attenuation in the BPA-mediated upregulation of Npy mRNA, suggesting that these antioxidant species in NBA potentially protect the cells from the detrimental effects of BPA. On another front, since BPA is considered an estrogen mimic in other cell types, we also investigated the involvement of estrogen receptors. BPA altered the ERβ/ERα ratio, decreasing it in the mHypoA-59 and mHypoE-41 cells, while increasing it in the mHypoE-46 cells due to a substantial decrease in ERα mRNA levels. Pretreatment with ERα or ERβ inhibitors (MPP, PHTPP, ICI182) did not alter the BPA-mediated upregulation of Npy, suggesting estrogen receptor-independent mechanisms mediate the increase in Npy. Future experiments will investigate whether estrogen receptors, particularly ERβ, mediate the BPA-induced downregulation of Npy in specific sub-populations. Overall, these experiments illustrate the mechanisms underlying the differential regulation of Npy by BPA in diverse neuronal sub-populations that may carry out distinct functions.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".