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In vivo changes in zebrafish anesthetic sensitivity in response to the loss of kif5Aa are associated with the alteration of mitochondrial motility.

Overview

Authors: Priya Dubey1, Roshni Datta1, Roderic G Eckenhoff1, Victoria M Bedell1
  1. Department of Anaesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
Institutions: University of Pennsylvania (United States)
Journal: PloS one, volume 21, issue 7, article e0316959
Dates: received 18 December 2024; accepted 6 May 2026; published online 27 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1371/journal.pone.0316959 · PMID 42507715 · PMCID PMC13405282 · OpenAlex W4405669006
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: zebrafish (organism), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions
MeSH: Anesthetics*, Kinesins*, Mitochondria*, Zebrafish*, Zebrafish Proteins*, Animals, Behavior, Animal, Gene Knockout Techniques, Larva, Neurons (* major topic)
Topic: Mitochondrial Function and Pathology (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: University of Pennsylvania; Center for Undergraduate Research and Scholarship, Bowling Green State University; National Institute of General Medical Sciences (GM13651, RM1 GM13651)
Citations: not cited yet (Europe PMC); 37 references in the paper

Abstract

Anesthetic and sedative drugs are small compounds known to bind to hundreds of proteins. One intriguing binding partner of propofol is the motor domain of a neuronal mitochondrial transport kinesin, kif5A. Here, we used zebrafish wild type (WT) and kif5Aa knockout (KO) larval behavioral assays to assess anesthetic sensitivity and combined that with zebrafish primary neuronal cell culture to probe for alterations in mitochondrial motility. We found that the loss of kif5Aa increases behavioral sensitivity to propofol and etomidate, with etomidate hypersensitivity greater than propofol. In contrast, kif5Aa KO animals were resistant to the behavioral effects of dexmedetomidine. Finally, WT and kif5Aa KO larvae responded similarly to the behavioral effects of ketamine. Propofol inhibited the anterograde motility of mitochondria in WT zebrafish neurons, while etomidate inhibited mitochondrial motility in both anterograde and retrograde directions; neither drug altered mitochondrial motility in the kif5Aa knockout (KO) neurons. In contrast, dexmedetomidine enhanced retrograde mitochondrial motility in both WT and kif5Aa KO animals. Finally, ketamine had little significant effect on mitochondrial motility in either mutant or WT animals. These data demonstrate that each anesthetic/sedative drug affects the motor protein machinery uniquely and is associated with unique changes in behavior. Understanding how different anesthetic compounds alter neuron motor proteins will be important in defining how anesthetics alter neuronal signaling and energetic dynamics.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data Availability

Data is available at https://doi.org/10.5061/dryad.x3ffbg808.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 2, 28 September 2026

  • Funding: added University of Pennsylvania; Center for Undergraduate Research and Scholarship, Bowling Green State University; National Institute of General Medical Sciences: GM13651, RM1 GM13651

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 10 MeSH terms, 36 references.

Cite

This paper

Dubey, P., Datta, R., Eckenhoff, R. G., & Bedell, V. M. (2026). In vivo changes in zebrafish anesthetic sensitivity in response to the loss of kif5Aa are associated with the alteration of mitochondrial motility. PloS one, 21(7), e0316959. https://doi.org/10.1371/journal.pone.0316959

BibTeX

@article{dubey2026vivo,
author = {Dubey, Priya and Datta, Roshni and Eckenhoff, Roderic G and Bedell, Victoria M},
title = {{In vivo changes in zebrafish anesthetic sensitivity in response to the loss of kif5Aa are associated with the alteration of mitochondrial motility}},
journal = {PloS one},
year = {2026},
month = jul,
volume = {21},
number = {7},
pages = {e0316959},
publisher = {PLOS},
issn = {1932-6203},
doi = {10.1371/journal.pone.0316959},
url = {https://doi.org/10.1371/journal.pone.0316959},
pmid = {42507715},
pmcid = {PMC13405282}
}

RIS

TY - JOUR
AU - Dubey, Priya
AU - Datta, Roshni
AU - Eckenhoff, Roderic G
AU - Bedell, Victoria M
TI - In vivo changes in zebrafish anesthetic sensitivity in response to the loss of kif5Aa are associated with the alteration of mitochondrial motility
T2 - PloS one
J2 - PLoS One
PY - 2026
DA - 2026/07/27
VL - 21
IS - 7
SP - e0316959
SN - 1932-6203
PB - PLOS
DO - 10.1371/journal.pone.0316959
UR - https://doi.org/10.1371/journal.pone.0316959
LA - en
ER -

CSL-JSON

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