AGPAT4 is a Mitochondrial Lysophosphatidic Acid Acyltransferase that Regulates Learning and Memory in Mice
Bibliographic record
Abstract
We have previously characterized acylglycerophosphate acyltransferase 4 (AGPAT4) as a mitochondrial lysophosphatidic acid acyltransferase. We have also determined that AGPAT4 is important in the regulation of brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI), since levels of these glycerophospholipids were decreased significantly by 38%, 32%, and 52%, respectively, in the brains of Agpat4 −/− mice. We investigated whether there were any impairments in cognition that may occur due to the significant loss of these three major glycerophospholipid species in the brains of Agpat4 −/− mice. We tested the behaviour of Agpat4 −/− mice and found that they have impaired spatial learning and memory as compared to wildtype littermates when assessed using the Morris Water Maze (MWM). Mechanisms underlying this effect were studied. No differences in whole‐body physiological parameters including respiratory capacity, food intake, motion and activity, or respiratory exchange ratio were evident. Similarly, we did not detect any changes with loss of Agpat4 in the brain mitochondrial content, or in the function of mitochondrial complexes as assessed in isolated brain mitochondria using high‐resolution respirometry. And, finally, we found that downstream targets of polyphosphorylated PI‐mediated signaling were also unchanged. However, Agpat4 −/− mice did have a significantly lower brain content of the NMDA receptor subunits NR2A and NR2B, as well as the AMPA receptor subunit GluR1. Our findings indicate that neuronal membrane phospholipid content and composition are important in regulating NMDA and AMPA receptor content with implications for learning and memory. Support or Funding Information This work was supported by grants to RED from the Canada Foundation for Innovation – Leader's Opportunity Fund and Ontario Research Fund (Project#30259), and a Discovery Grant (#418213‐2012) from the Natural Sciences and Engineering Research Council (NSERC) of Canada. EBM is the recipient of an NSERC Master's Scholarship (PGS‐M). RMB, JJAH, ASM, DB, PMM are the recipients of an NSERC Doctoral Scholarship (PGS‐D).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 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".