P3–353: Orexinergic projections to acetylcholinesterase neurons in normal and Alzheimer forebrain
Bibliographic record
Abstract
Cholinergic and orexinergic neurotransmitter systems are both involved in arousal and sleep–wakefulness cycles. In Alzheimer's disease (AD), there is significant loss of cholinergic neurons that leads to salient cognitive and behavioural symptoms. Patients with AD have disturbances in sleep patterns that can cause significant behavioural disturbances leading to patient and care–giver stress. In order to understand possible mechanism(s) of sleep disturbance in these patients, we examined the relationship of orexinergic projections to cholinergic neurons in normal forebrain and in AD. Immunoreactivity for orexin A and B was assessed in human brain from 4 control subjects without neuropathology (ages: 70–77) and from 4 clinically and neuropathologically confirmed AD patients (ages: 70–92). Goat polyclonal antibodies raised against human orexin A or orexin B (Santa Cruz Biotechnology) were used and the immunohistochemical reaction was visualized using the avidin–biotin–diaminobenzidine method. Sections were also stained for acetylcholinesterase (AChE) and Nissl substance. In both control and AD brains, orexin–positive cell bodies were found in the lateral, perifornical and medial regions of the hypothalamus. In the thalamus, orexinergic projections specifically target magnocellular cell groups that also receive dense cholinergic innervation (Heckers et al., 19920 and are AChE–positive (Darvesh and Hopkins, 2003). These include magnocellular cell groups of the medial dorsal, intralaminar and cucullar nuclei as well as the limitans–suprageniculate complex. Orexin–positive axons were in close proximity to large, hyperchromic neurons, many of which stain for AChE. Similarly, in the basal forebrain, dense orexinergic projections selectively targeted the large, hyperchromic cholinergic neurons of the nucleus basalis, as well as neurons of the nucleus of the diagonal band of Broca, most of which were also AChE–positive. These cell groups project to the cerebral cortex and subcortical forebrain structures such as the hippocampal formation and amygdala. The distribution of orexin in the human forebrain is consistent with their role in arousal and the regulation of the sleep–wake cycle. Qualitative observations suggest that orexinergic innervation may be altered in AD brains.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.005 | 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".