Neurotrophins as intercellular signaling molecules of the brain regulate select immune functions of microglia
Bibliographic record
Abstract
Microglia are the resident immune cells of the brain, which become activated in response to diverse immune stimuli. Following activation, microglia signal to other central nervous system (CNS) cells by secreting a variety of cytokines. Under specific stimulatory conditions, microglia can also release a spectrum of cytotoxins, including reactive oxygen species (ROS), reactive nitrogen species (RNS), proteases, and other enzymes. Molecules secreted by microglia have specific functions in the neuroimmune response to pathogens and endogenous stimuli. They also contribute to the pathogenesis of neurodegenerative diseases. Neurotrophins (NTs) are proteins that support development, maturation and normal metabolic functions of neurons by interacting with neurotrophin receptors (NTRs) on these cells. Microglia also express several NTRs that signal in response to binding of NTs. These include tropomyosin receptor kinase (Trk)A, TrkB and p75NTR. Binding and activation of these receptors can alter the phenotype, metabolism, and other functions of microglia. We hypothesized that NTR ligands, such as the small molecule ligand LM11A-31 and the NT precursor pro-brain derived neurotrophic factor (proBDNF), bind p75NTR and modulate the immune functions of microglia. We studied the effects of NTR ligands on the following immune functions by using in vitro models of microglia: 1) secretion of cytotoxins and cytokines by lipopolysaccharide (LPS) plus interferon-γ stimulated human THP-1 monocytic cells; 2) release of ROS through the LPS-primed respiratory burst response of dimethyl sulfoxide-differentiated human HL-60 myelomonocytic cells; 3) secretion of nitric oxide by LPS-stimulated murine BV-2 microglia; and 4) phagocytic activity of BV-2 cells. LM11A-31 and proBDNF inhibited the respiratory burst response of differentiated HL-60 microglia-like cells but did not have a significant effect in most other cellular assays. Our data indicate that NTs could serve as intercellular signaling molecules of the CNS by regulating select immune functions of microglia, such as their production of ROS.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".