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Loss of Panx1 Function in Zebrafish Alters Motor Behavior in a Lab-on-Chip Model of Parkinson's Disease

2022· preprint· en· W4311798060 on OpenAlexafffund
Arezoo Khalili, Nickie Safarian, Ellen van Wijngaarden, Georg Zoidl, Pouya Rezai

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicConnexins and lens biology
Canadian institutionsYork University
FundersNatural Sciences and Engineering Research Council of CanadaFondation Brain Canada
KeywordsZebrafishTyrosine hydroxylaseDopaminergicBiologyParkinson's diseaseDopamineNeuroscienceInternal medicineCell biologyDiseaseMedicineBiochemistryGene

Abstract

fetched live from OpenAlex

Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play essential roles in purinergic signaling in the nervous system. Several studies suggest a link between Panx1-based channels activity and neurodegenerative disorders including Parkinson’s disease (PD), but experimental evidence is limited. Here, we applied behavioral and molecular screening of zebrafish larvae to examine the role of Panx1 in both pathological and normal conditions, using electrical stimulation in a microfluidic chip and RT-qPCR. A zebrafish model of PD was produced by exposing wildtype (panx1a+/+) and Panx1a knock-out (panx1a-/-) zebrafish larvae to 250µM 6-hydroxydopamine (6-OHDA). After 72hrs treatment with 6-OHDA a reduced electric-induced locomotor activity was observed in 5 days post fertilization (dpf) panx1a+/+ larvae. The 5dpf panx1a-/- larvae were not different from affected. The RT-qPCR data showed a reduction in tyrosine hydroxylase (TH) expression level in both panx1a+/+ and panx1a-/- groups. However, TH expression of 6-OHDA exposed panx1a-/- larvae was not decreased when compared to untreated mutants. Extending 6-OHDA treatment duration to 120hrs caused a significant reduction in the locomotor response of 7dpf panx1a-/- larvae when compared to the untreated panx1a-/- group. The RT-qPCR data also confirmed a significant decrease in TH expression levels after 120hrs treatments with 6-OHDA for both genotypes. Our results suggest that the absence of Panx1a channels compromised dopaminergic signaling in 6-OHDA-treated zebrafish larvae. We here propose that zebrafish Panx1a models offer great opportunities to shed light on the physiological and molecular basis of PD. Panx1a might play a preventive role on PD progression, and therefore deserves further investigation

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 score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
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 head0.019
GPT teacher head0.255
Teacher spread0.236 · 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

Citations0
Published2022
Admission routes2
Has abstractyes

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