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Record W3211870305 · doi:10.1101/2021.11.12.468443

New neurons in old brains: A cautionary tale for the analysis of neurogenesis in post-mortem tissue

2021· preprint· en· W3211870305 on OpenAlexafffund
Dylan J. Terstege, Kwaku Addo-Osafo, G. Campbell Teskey, Jonathan R. Epp

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldNeuroscience
TopicNeurogenesis and neuroplasticity mechanisms
Canadian institutionsUniversity of Calgary
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Open Neuroscience PlatformUniversity of Calgary
KeywordsNeurogenesisSubventricular zoneSubgranular zoneHippocampusBiologyNeuroscienceFixation (population genetics)RodentBrain tissueMammalian brainNeural stem cellStem cellCell biologyGenetics

Abstract

fetched live from OpenAlex

Abstract Adult neurogenesis has primarily been examined in two key regions in the mammalian brain, the subgranular zone of the hippocampus and the subventricular zone. The proliferation and integration of newly generated neurons has been observed widely in adult mammalian species including the human hippocampus. Recent high-profile studies have suggested however, that this process is considerably reduced in humans, occurring in children but declining rapidly and nearly completely in the adult brain. In comparison, rodent studies also show age-related decline but a greater degree of proliferation of new neurons in adult animals. Here, we examine whether differences in tissue fixation, rather than biological difference in human versus rodent studies might account for the diminished levels of neurogenesis sometimes observed in the human brain. To do so we analyzed neurogenesis in the hippocampus of rats that were either perfusion-fixed or the brains extracted and immersion-fixed at various post-mortem intervals. We observed an interaction between animal age and the time delay between death and tissue fixation. While similar levels of neurogenesis were observed in young rats regardless of fixation, older rats had significantly fewer labeled neurons when fixation was not immediate. Furthermore, the morphological detail of the labeled neurons was significantly reduced in the delayed fixation conditions at all ages. This study highlights critical concerns that must be considered when using post-mortem tissue to quantify adult neurogenesis.

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 imitation

Not 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.

metaresearch head score (Codex)0.023
metaresearch head score (Gemma)0.039
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.023
Threshold uncertainty score0.124

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0230.039
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.001
Bibliometrics0.0040.002
Science and technology studies0.0030.011
Scholarly communication0.0030.006
Open science0.0040.004
Research integrity0.0030.017
Insufficient payload (model declined to judge)0.0040.004

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.

Opus teacher head0.025
GPT teacher head0.248
Teacher spread0.223 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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".

Quick stats

Citations3
Published2021
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicNeurogenesis and neuroplasticity mechanisms→French-language works237,207→