Hippocampal Synaptic Dysfunction in a Mouse Model of Huntington Disease Is Not Alleviated by Ceftriaxone Treatment
Bibliographic record
Abstract
Glutamate transporters, particularly glutamate transporter 1 (GLT-1), help to prevent the adverse effects associated with glutamate toxicity by rapidly clearing glutamate from the extracellular space. Since GLT-1 expression and/or function are reduced in many neurodegenerative diseases, upregulation of GLT-1 is a favorable approach to treat the symptoms of these diseases. Ceftriaxone, a β-lactam antibiotic reported to increase GLT-1 expression, can exert neuroprotective effects in a variety of neurodegenerative diseases; however, many of these diseases do not exhibit uniform brain pathology. In contrast, as a drug that readily crosses the blood-brain barrier, ceftriaxone administration is likely to increase GLT-1 levels globally throughout the neuroaxis. In Huntington disease (HD), low GLT-1 expression is observed in the striatum in postmortem tissue and animal models. While ceftriaxone was reported to increase striatal GLT-1 and ameliorate the motor symptoms in a mouse model of HD, the extrastriatal effects of ceftriaxone in HD are unknown. Using electrophysiology and high-speed imaging of the glutamate biosensor iGluSnFR, we quantified real-time glutamate dynamics and synaptic plasticity in the hippocampus of the Q175FDN mouse model of HD, following intraperitoneal injections of either saline or ceftriaxone. We observed an activity-dependent increase in extracellular glutamate accumulation within the HD hippocampus, which was not the result of reduced GLT-1 expression. Surprisingly, ceftriaxone had little effect on glutamate clearance rates and negatively impacted synaptic plasticity. These data provide evidence for glutamate dysregulation in the HD hippocampus but also caution the use of ceftriaxone as a treatment for HD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 teacher head, 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".