Lithium mitigates hippocampal tau pathology in a rodent model of traumatic brain injury
Bibliographic record
Abstract
Repetitive traumatic brain injury (TBI) is the main risk factor for chronic traumatic encephalopathy (CTE), a neurodegenerative disease that is defined by pathological inclusions of phosphorylated tau protein located at the depths of the cortical sulci and surrounding blood vessels. The cellular mechanisms involved in tau phosphorylation are upregulated by TBI, leading to increased levels of misfolded tau, which can progress to form insoluble aggregates and drive the progression of CTE. Targeting tau phosphorylation is thus an appealing strategy for reducing tau aggregation and preventing CTE. The phosphorylation of tau at Thr231 is a crucial step that promotes aberrant tau misfolding and fibril formation that occurs following TBI and in CTE. Lithium, known for its neuroprotective effects, has previously been shown to reduce tau phosphorylation. However, its effect on Thr231 in the context of TBI is unknown. In this study, we investigated the therapeutic potential of lithium on tau phosphorylation in a rodent model of TBI. Female adult rats subjected to a single TBI were administered daily lithium and histologically assessed for tau pathology, neuroinflammation, and neurodegeneration. In TBI animals, pThr231 tau pathology progressively increased throughout the hippocampus over the first 10 days and was associated with a loss of Calbindin 1 and an increase in mitochondrial calcium uniporter (MCU) expression. Lithium treatment reduced hippocampal pThr231 tau pathology and microgliosis at day 10 post-TBI. In lithium-treated TBI animals, the loss of Calbindin 1 was prevented and the level of MCU was decreased in regions associated with reduced pThr231 tau pathology. In CTE, the level of Calbindin 1 was similarly decreased in the presence of pThr231-positive neurofibrillary tangles. These findings demonstrate that lithium is effective in reducing hippocampal pThr231 tau pathology and attenuating neuroinflammation in TBI, accompanied by maintaining physiological expression of Calbindin 1 and MCU.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".