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Sustained AMPAR expression in CA3 neurons may mediate neuroprotection following FLASH-RT.

Overview

Authors: Louis V. Kunz1,2,3, Aymeric Almeida1,2,3, Michèle Knol1,2, Benoît Petit1,2,4, Enikö A. Kramár5, Marcelo A. Wood5, Charles L. Limoli6, Marie-Catherine Vozenin1,2,4,7
  1. Radiotherapy and Radiobiology Sector, Radiation Therapy Service, University Hospital of Geneva, Geneva, Switzerland
  2. LiRR - Laboratory of Innovation in Radiobiology Applied to Radiotherapy/Faculty of Medicine/University of Geneva, Geneva, Switzerland
  3. These authors contributed equally
  4. Radiation Oncology Laboratory, University Hospital and University of Lausanne, Lausanne, Switzerland
  5. Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697, USA
  6. Department of Radiation Oncology, University of California, Irvine, Irvine, CA 92697, USA
  7. Lead contact
Institutions: University of Geneva (Switzerland); University Hospital of Geneva (Switzerland); University of Lausanne (Switzerland); University of California, Irvine (United States)
Journal: Cell reports, volume 45, issue 7, article 117670
Dates: published online 13 July 2026; in print 28 July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.celrep.2026.117670 · PMID 42441406 · PMCID PMC13584352 · OpenAlex W7168153936
Open access: gold, a free copy (OpenAlex)
Status: dead link
Categories: genetics / omics (modality), mouse (organism), cellular / molecular (subfield)
Methods: Smoothing, state filtering, decompositions, Statistics, fMRI & imaging
Keywords: Calcium, Hippocampus, Neuron, Cognition, Glutamate receptor, Radiotherapy, flash, Ampar, Transcriptomics, Ca3, Cp: Neuroscience
MeSH: CA3 Region, Hippocampal*, Neurons*, Neuroprotection*, Receptors, AMPA*, Animals, Dentate Gyrus, Male, Mice, Mice, Inbred C57BL (* major topic)
Topic: Neuroscience and Neuropharmacology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Swiss Cancer Research Foundation; NCI NIH HHS (R01 CA254892, P01 CA244091); Swiss Cancer League (KFS 5757-02-2023); National Institutes of Health (P01CA244091-01, R01CA254892-1)
Citations: not cited yet (Europe PMC); 57 references in the paper
Research resources: Anti NeuN RRID:AB_10807945, Anti-CD31 Alexa 488 RRID:AB_10972784, Rabbit anti-Camk2 alpha RRID:AB_11157799, Rabbit anti-GluA2/Gria2 RRID:AB_2039881, AF488 Dk-aRb RRID:AB_2535792, AF555 Dk-aMs RRID:AB_2536180, Goat anti-rabbit Alexa 594 RRID:AB_2650602, Guinea pig anti-GluN1/Grin1 RRID:AB_2756610, Mouse anti-Phospho-CaMKII alpha (Thr286) RRID:AB_325402, Anti-Gfap Alexa 647 RRID:AB_3284407, Goat F(ab) Anti-Mouse RRID:AB_955960, C57Bl/6 J RRID:IMSR_JAX:000664

Abstract

To elucidate the early mechanisms underlying the long-term neuroprotective effect of FLASH-RT in the normal brain, spatial transcriptomics (Nanostring) were performed after whole-brain irradiation of C57BL/6J mice with either 1 or 3 fractions of 10 Gy at 5.6 × 106 Gy/s (1 pulse-FLASH) or at conventional dose-rate 0.1 Gy/s. FLASH-RT induced a distinct transcriptomic signature in the cornu ammonis region 3 (CA3) and dentate gyrus (DG) neurons, with upregulation of genes encoding glutamate receptors involved in calcium signaling, long-term potentiation, and mitochondrial OXPHOS. Early transcriptional upregulation of Gria genes translated into increased AMPAR protein levels at 48 h in the DG and CA3 region and sustained higher AMPAR expression at 2 and 4 weeks post-FLASH. These findings support a durable activation of AMPAR. We propose a mechanism to explain FLASH-induced neuroprotection initiated by early calcium influx and subsequent sustained expression of glutamate AMPARs in neurons and/or neural progenitors of the CA3, potentially contributing to long-term cognitive sparing.

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

Code

No file of the authors' code could be read here: it is described below, and read at its source.

gitlab.unige.ch/lirr/nanostring_flash_mouse_brain

License: none: the authors keep all their rights
State: the link is dead, verified on 27 September 2026
Evidence: found in the paper
Software Heritage: not archived
Found in: “Data and code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link is dead
  • 27 September 2026: the link is dead

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 0 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data and code availability

Data: raw and processed Nanostring GeoMx DSP data are publicly available as of the date of publication in Gene Expression Omnibus (GEO) under accession number GSE305149 as referenced in key resources table, deposited data section. Immunofluorescence data can be made available upon request.

Code: all scripts used for the analysis are available at https://gitlab.unige.ch/lirr/nanostring_flash_mouse_brain as of the date of publication.

Other items: any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: n/a → Cell Press

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 11 keywords, 9 MeSH terms, 4 funders, 44 references, 12 RRIDs.

Cite

This paper

Kunz, L. V., Almeida, A., Knol, M., Petit, B., Kramár, E. A., Wood, M. A., Limoli, C. L., & Vozenin, M.-C. (2026). Sustained AMPAR expression in CA3 neurons may mediate neuroprotection following FLASH-RT. Cell reports, 45(7), 117670. https://doi.org/10.1016/j.celrep.2026.117670

BibTeX

@article{kunz2026sustained,
author = {Kunz, Louis V. and Almeida, Aymeric and Knol, Michèle and Petit, Benoît and Kramár, Enikö A. and Wood, Marcelo A. and Limoli, Charles L. and Vozenin, Marie-Catherine},
title = {{Sustained AMPAR expression in CA3 neurons may mediate neuroprotection following FLASH-RT}},
journal = {Cell reports},
year = {2026},
month = jul,
volume = {45},
number = {7},
pages = {117670},
publisher = {Cell Press},
issn = {2211-1247},
doi = {10.1016/j.celrep.2026.117670},
url = {https://doi.org/10.1016/j.celrep.2026.117670},
pmid = {42441406},
pmcid = {PMC13584352}
}

RIS

TY - JOUR
AU - Kunz, Louis V.
AU - Almeida, Aymeric
AU - Knol, Michèle
AU - Petit, Benoît
AU - Kramár, Enikö A.
AU - Wood, Marcelo A.
AU - Limoli, Charles L.
AU - Vozenin, Marie-Catherine
TI - Sustained AMPAR expression in CA3 neurons may mediate neuroprotection following FLASH-RT
T2 - Cell reports
J2 - Cell Rep
PY - 2026
DA - 2026/07/13
VL - 45
IS - 7
SP - 117670
SN - 2211-1247
PB - Cell Press
DO - 10.1016/j.celrep.2026.117670
UR - https://doi.org/10.1016/j.celrep.2026.117670
LA - en
ER -

CSL-JSON

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