P1–393: Quantification of inositol in the brain and CSF of TgCRND8 mice
Bibliographic record
Abstract
Our previous in vitro work found that inositol stereoisomers were able to prevent AÎ fibrillization to varying degrees. The AΖinositol interaction resulted in small AÎ42 aggregates but only decreased the kinetics of AÎ40 assembly (McLaurin et al, 2000, JBC). Furthermore, the effective isomers were able to disaggregate preformed AÎ fibres. Inositol is a simple polyol with eight naturally occurring stereoisomers and has been shown to be elevated in AD brain. Given these findings, we investigated whether inositol isomers could cross the blood–brain barrier and subsequently increase the steady–state brain inositol levels. 1. To determine whether the concentration of inositol is altered in the brain after peripheral administration. We hypothesize that the peripheral administration of inositol stereoisomers will result in an increased concentration of these compounds in the cerebral spinal fluid and the brain. 2. Determine whether this results in increased incorporation into phosphoinositides or the phosphatidylinositol family of lipids. To test this hypothesis, gas chromatography/mass spectrometry was used to measure inositol levels in the brain and the cerebral spinal fluid after oral dose administration. To increase the volatility and thermal stability of these compounds and to allow for proper peak separation the hydroxyl groups of inositol were derivatized with acetyl groups (adapted from Shetty Hu et al, 1995, Anal Biochem 224:279–285). We found improved quantification of inositol by monitoring mass ion 168. Inositol levels in phosphatidylinositol lipids and phosphoinositides were quantified by inositol isolation using thin layer chromatography and acid hydrolysis (Kersting et al, 2003, J Eukaryot Microbiol) followed by gas chromatography/mass spectrometry. Peripherally administered inositols showed a rapid increase in plasma inositol levels as monitored by radioactively labeled inositol compounds. Continuous administration of some inositols increased concentrations in both brain and CSF. The increase in inositol levels did not alter phosphoinositide levels nor incorporation of peripherally administered inositol into phosphatidylinositol family of lipids. Dose response increases were observed for the most effective inositol isomers. These results show that peripheral administration dose dependently increases brain steady state inositol levels.Molecular Mechanisms of Neurodegeneration Others
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".