Component
Ganaxolone, a synthetic neurosteroid
Ganaxolone, a synthetic neurosteroid. Species, exposure and limitations are retained in each linked claim.
1 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
Where it participates (unsigned role)
Zinc is an abundant trace metal in the hippocampus nerve terminals and blocked the GABA-evoked and ganaxolone-potentiated GABA-gated chloride currents in dentate gyrus granule cells and CA1 pyramidal cells in a concentration-dependent fashion similar to competitive GABA-A receptor antagonists, zinc completely blocked ganaxolone potentiation of extrasynaptic tonic currents but not synaptic phasic currents, systemic ganaxolone produced dose-dependent suppression of behavioral and electrographic seizures in fully-kindled mice with complete protection at 10 mg/kg, however the antiseizure effects were significantly prevented by intrahippocampal zinc with a median effective dose of 150 micromolar, and the response was reversible.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/gaba-research/30471294.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a", "start_char": 0, "end_char": 1814, "text_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a"}
- experimental_model
- Recordings of tonic and phasic currents in dissociated hippocampal neurons and slices, with a kindled seizure model
- exposure
- Zinc with the synthetic neurosteroid ganaxolone, applied to neurons and intrahippocampally in fully kindled mice
- limitations
- The separation of tonic from phasic current is what makes the subunit assignment work. Zinc was given intrahippocampally at a defined dose rather than altered nutritionally.
- nutrient_topic
- GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid
- organism
- Mouse
- plain_language
- Zinc shuts down the steroid-sensitive receptors that sit outside synapses while leaving the ones inside synapses working.
- primary_references
- [gb-p30471294] Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus. (2019). https://pubmed.ncbi.nlm.nih.gov/30471294/ DOI: 10.1016/j.neuropharm.2018.11.031
- tissue_or_cell_type
- Dentate gyrus granule cells and CA1 pyramidal cells
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recordings of tonic and phasic currents in dissociated hippocampal neurons and slices, with a kindled seizure model · source_derived_draft · unverified_draft
### gb-zinc-blocks-only-the-tonic-receptors Zinc is an abundant trace metal in the hippocampus nerve terminals and blocked the GABA-evoked and ganaxolone-potentiated GABA-gated chloride currents in dentate gyrus granule cells and CA1 pyramidal cells in a concentration-dependent fashion similar to competitive GABA-A receptor antagonists, zinc completely blocked ganaxolone potentiation of extrasynaptic tonic currents but not synaptic phasic currents, systemic ganaxolone produced dose-dependent suppression of behavioral and electrographic seizures in fully-kindled mice with complete protection at 10 mg/kg, however the antiseizure effects were significantly prevented by intrahippocampal zinc with a median effective dose of 150 micromolar, and the response was reversible. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: Zinc shuts down the steroid-sensitive receptors that sit outside synapses while leaving the ones inside synapses working. organism: Mouse tissue_or_cell_type: Dentate gyrus granule cells and CA1 pyramidal cells experimental_model: Recordings of tonic and phasic currents in dissociated hippocampal neurons and slices, with a kindled seizure model limitations: The separation of tonic from phasic current is what makes the subunit assignment work. Zinc was given intrahippocampally at a defined dose rather than altered nutritionally. exposure: Zinc with the synthetic neurosteroid ganaxolone, applied to neurons and intrahippocampally in fully kindled mice evidence_span: {"source_cache": "artifacts/gaba-research/30471294.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a", "start_char": 0, "end_char": 1814, "text_sha256": "657923c781b7e3a3309235bce60303fde53f18d7a830cde050b268269f02747a"} [gb-p30471294] Zinc reduces antiseizure activity of neurosteroids by selective blockade of extrasynaptic GABA-A receptor-mediated tonic inhibition in the hippocampus. (2019). https://pubmed.ncbi.nlm.nih.gov/30471294/ DOI: 10.1016/j.neuropharm.2018.11.031
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.