Observations of the Morphological Evolution of Neuronal Intranuclear Rods in the Human Substantia Nigra Across the Age Spectrum
Bibliographic record
Abstract
Abstract Objectives Parkinson’s disease (PD) is a neurodegenerative disease characterized by a depletion of dopaminergic neurons in the substansia nigra (SN). Loss of SN neurons occurs at a rate of up to 10% per decade in nonpathological aging. Other age-related changes in nigral neurons include accumulation of intranuclear inclusions called Marinesco bodies (MBs). MBs have been shown to associate with a distinct type of neuronal intranuclear body called the intranuclear rod (INR). At what point in the aging process INRs develop, and when they give rise to MBs, are questions that remain unanswered. In this observational study, we set out to determine whether SN INRs display changes in their morphology across the human age spectrum. Methods The laboratory information system was searched for hospital and forensic autopsies conducted from 2010-2017 that had midbrain sections taken. Ten slides were cut from each of 11 age groups from ages ranging from 1 month to 80 years of age. Sections were immunostained with glucocorticoid receptor (GR) to identify INRs. Results There was a progressive age-associated transition in INR morphology from long, linear intranuclear structures in the youngest age groups (infants), to shorter linear structures at middle ages, culminating in small, dot-like juxtanucleolar structures in elderly subjects. A proportion of short INRs displayed contact with MBs in the middle age groups. Conclusion We demonstrated a striking progressive, age-dependent alteration in INR morphology. These results suggest that INRs give rise to MBs in the SN during middle ages. As a follow-up of this preliminary observational study, quantitative analysis of INR frequency and size is currently being performed in our lab. Ultimately, we plan to expand our cases for the creation of a human SN tissue microarray, which we hope will shed light on the cellular mechanisms of neuronal ageing and degeneration in the SN.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 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) | 0.001 | 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".