The effect of hearing loss on a rat model with genetic susceptibility to Alzheimer's disease
Bibliographic record
Abstract
BACKGROUND: Dementia affects ∼55 million people worldwide; a staggering statistic which highlights the need to limit its risk factors. Cognitive decline and sensory gating deficits are all hallmark of Alzheimer's disease (AD), and are thought to be mediated in part by several neuropathological changes within the brain including synaptic loss in the cerebral cortex and hippocampus. Importantly, epidemiological studies have identified hearing loss as a major modifiable risk factor for the development of dementia, including AD. However, the mechanisms by which hearing loss interacts with genetic susceptibility to increase the risk of developing AD is poorly understood. METHODS: In the present study, we investigated the effect of hearing loss on cognitive function, sensory gating, and hippocampal synaptic density in a rat model with genetic susceptibility to AD. Fischer 344 (TgAPP) rats represent a prodromal model of AD, as they overexpress pathogenic human amyloid precursor protein, but do not spontaneously develop β-amyloid plaques. At 15 months of age, TgAPP male rats were noise-exposed (12 kHz, 110 dB SPL, 3 hours) to generate hearing loss, with sham-exposed wildtype and TgAPP rats utilized as controls. Cognitive function was assessed using the Morris water maze task, with hippocampal synaptic density quantified through Golgi-Cox staining. Sensory gating was assessed behaviourally using pre-pulse inhibition of the acoustic startle reflex and electrophysiologically with an auditory paired pulse paradigm. RESULTS: Consistent with hearing loss often experienced by humans, our protocol resulted in high-frequency hearing loss in the rats. As expected, TgAPP rats exhibited impaired reference memory compared to the wildtype rats; however, this was not exacerbated by hearing loss. While behavioural sensory gating remained unchanged, our preliminary electrophysiological results revealed genotype-specific differences in auditory gating. Lastly, we observed an increase in spine density on basal dendrites of hippocampal CA1 neurons in noise-exposed animals. CONCLUSION: Ultimately, our preclinical data help provide novel insight into the interplay between hearing loss and genetic susceptibility to AD. Collectively, our results demonstrate that while AD-related impairments were evident in our prodromal model of AD, the degree of noise-induced hearing loss used in the present study was insufficient to exacerbate these impairments.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".