3-C-343 - Glutamate uptake asymmetry in a mouse model of alzheimer disease
Bibliographic record
Abstract
Authors: Kyle Brymer¹, Jocelyn Barnes¹, Matthew Parsons² ¹Memorial University, ²Memorial University of Newfoundland Abstract: Sodium-dependent high affinity glutamate transporters are essential in mitigating the toxic effects of extracellular glutamate accumulation. Glutamate uptake is primarily mediated by astrocytes, although glial coverage is reported to be four times higher postsynaptically than presynaptically. The functional consequences of this synapse asymmetry in glial coverage is poorly understood, but it implies the presynapse is more vulnerable to glutamate uptake impairments than the postsynapse in brain diseases with compromised glutamate uptake, such as Alzheimer disease (AD). Here, we developed a novel approach to quantify the unique glutamate clearance dynamics in presynaptic and postsynaptic microenvironments in the hippocampus of the 3xTg mouse model of AD through a combination of intensity-based glutamate sensing fluorescent reporter (iGluSnFR) and two-photon microscopy. By 6-months, an age corresponding to the emergence of an AD-like phenotype in the 3xTg mouse, glutamate clearance in presynaptic microenviornments was impaired while clearance in postsynaptic microenvironments was unimpaired in 3xTg mice. This impairment is mediated by GLT-1 as confirmed by 2 observations: DHK application to acute hippocampal slices increases glutamate clearance time in presynaptic microenvironments, but the extent of this increase is lesser in 3xTg mice compared to control mice; and EAAT2 overexpression via ceftriaxone speeds up glutamate clearance in presynaptic microenvironments. This implies that glutamate transporters have different capabilities depending on the specific microenvironment within a given region, and in the context of AD, suggests that the emergence of presynaptic microenvironment glutamate clearance deficits may correlate with the emergence of AD-like synaptic pathology
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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) | 0.001 | 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 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".