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Record W4387333859 · doi:10.7554/elife.90893

Increasing adult-born neurons protects mice from epilepsy

2023· article· en· W4387333859 on OpenAlexaff
Swati Jain, John J. LaFrancois, Kasey Gerencer, Justin J. Botterill, Meghan Kennedy, Chiara Criscuolo, Helen E. Scharfman

Bibliographic record

VenueeLife · 2023
Typearticle
Languageen
FieldNeuroscience
TopicNeurogenesis and neuroplasticity mechanisms
Canadian institutionsUniversity of Saskatchewan
FundersNational Institute of Neurological Disorders and StrokeNational Institute on AgingNational Institutes of HealthNew York State Office of Mental Health
KeywordsEpileptogenesisEpilepsyNeurogenesisDentate gyrusStatus epilepticusHippocampal formationPilocarpineNestinConvulsantNeuroscienceEndocrinologyNeuroprotectionMedicineInternal medicineBiologyStem cellNeural stem cellReceptorCell biology

Abstract

fetched live from OpenAlex

Neurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic life-long seizures (epilepsy), we asked if increasing adult-born neurons would prevent epilepsy. Adult-born neurons were selectively increased by deleting the pro-apoptotic gene Bax from Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally delete Bax in Nestin-CreER T2 Bax fl/fl mice. Six weeks after tamoxifen administration, severe seizures (status epilepticus; SE) were induced by injection of the convulsant pilocarpine. After mice developed epilepsy, seizure frequency was quantified for 3 weeks. Mice with increased adult-born neurons exhibited fewer chronic seizures. Postictal depression was reduced also. These results were primarily in female mice, possibly because they were more affected by Bax deletion than males, consistent with sex differences in Bax . The female mice with enhanced adult-born neurons also showed less neuronal loss of hilar mossy cells and hilar somatostatin-expressing neurons than wild-type females or males, which is notable because loss of these two hilar cell types is implicated in epileptogenesis. The results suggest that selective Bax deletion to increase adult-born neurons can reduce experimental epilepsy, and the effect shows a striking sex difference. The results are surprising in light of past studies showing that suppressing adult-born neurons can also reduce chronic seizures.

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)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.001

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.

Opus teacher head0.038
GPT teacher head0.260
Teacher spread0.222 · 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 designBench or experimental
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

Citations5
Published2023
Admission routes1
Has abstractyes

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