Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity

The deep space environment contains many risks to astronauts during space missions, such as galactic cosmic rays (GCRs) comprised of naturally occurring heavy ions. Heavy ion radiation is increasingly being used in cancer therapy, including novel regimens involving carbon therapy. Previous investiga...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sydney Weber Boutros, Benjamin Zimmerman, Sydney C. Nagy, Joanne S. Lee, Ruby Perez, Jacob Raber
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	amifostine heavy ion radiation cognition cFos sex differences Physiology QP1-981
Acceso en línea:	https://doaj.org/article/ab1d46c465bd4e8f8cb50b37ca5f511a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ab1d46c465bd4e8f8cb50b37ca5f511a
record_format	dspace
spelling	oai:doaj.org-article:ab1d46c465bd4e8f8cb50b37ca5f511a2021-11-16T11:14:55ZAmifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity1664-042X10.3389/fphys.2021.770502https://doaj.org/article/ab1d46c465bd4e8f8cb50b37ca5f511a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.770502/fullhttps://doaj.org/toc/1664-042XThe deep space environment contains many risks to astronauts during space missions, such as galactic cosmic rays (GCRs) comprised of naturally occurring heavy ions. Heavy ion radiation is increasingly being used in cancer therapy, including novel regimens involving carbon therapy. Previous investigations involving simulated space radiation have indicated a host of detrimental cognitive and behavioral effects. Therefore, there is an increasing need to counteract these deleterious effects of heavy ion radiation. Here, we assessed the ability of amifostine to mitigate cognitive injury induced by simulated GCRs in C57Bl/6J male and female mice. Six-month-old mice received an intraperitoneal injection of saline, 107 mg/kg, or 214 mg/kg of amifostine 1 h prior to exposure to a simplified five-ion radiation (protons, 28Si, 4He, 16O, and 56Fe) at 500 mGy or sham radiation. Mice were behaviorally tested 2–3 months later. Male mice that received saline and radiation exposure failed to show novel object recognition, which was reversed by both doses of amifostine. Conversely, female mice that received saline and radiation exposure displayed intact object recognition, but those that received amifostine prior to radiation did not. Amifostine and radiation also had distinct effects on males and females in the open field, with amifostine affecting distance moved over time in both sexes, and radiation affecting time spent in the center in females only. Whole-brain analysis of cFos immunoreactivity in male mice indicated that amifostine and radiation altered regional connectivity in areas involved in novel object recognition. These data support that amifostine has potential as a countermeasure against cognitive injury following proton and heavy ion irradiation in males.Sydney Weber BoutrosBenjamin ZimmermanBenjamin ZimmermanBenjamin ZimmermanSydney C. NagyJoanne S. LeeRuby PerezJacob RaberJacob RaberJacob RaberFrontiers Media S.A.articleamifostineheavy ion radiationcognitioncFossex differencesPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amifostine heavy ion radiation cognition cFos sex differences Physiology QP1-981
spellingShingle	amifostine heavy ion radiation cognition cFos sex differences Physiology QP1-981 Sydney Weber Boutros Benjamin Zimmerman Benjamin Zimmerman Benjamin Zimmerman Sydney C. Nagy Joanne S. Lee Ruby Perez Jacob Raber Jacob Raber Jacob Raber Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity
description	The deep space environment contains many risks to astronauts during space missions, such as galactic cosmic rays (GCRs) comprised of naturally occurring heavy ions. Heavy ion radiation is increasingly being used in cancer therapy, including novel regimens involving carbon therapy. Previous investigations involving simulated space radiation have indicated a host of detrimental cognitive and behavioral effects. Therefore, there is an increasing need to counteract these deleterious effects of heavy ion radiation. Here, we assessed the ability of amifostine to mitigate cognitive injury induced by simulated GCRs in C57Bl/6J male and female mice. Six-month-old mice received an intraperitoneal injection of saline, 107 mg/kg, or 214 mg/kg of amifostine 1 h prior to exposure to a simplified five-ion radiation (protons, 28Si, 4He, 16O, and 56Fe) at 500 mGy or sham radiation. Mice were behaviorally tested 2–3 months later. Male mice that received saline and radiation exposure failed to show novel object recognition, which was reversed by both doses of amifostine. Conversely, female mice that received saline and radiation exposure displayed intact object recognition, but those that received amifostine prior to radiation did not. Amifostine and radiation also had distinct effects on males and females in the open field, with amifostine affecting distance moved over time in both sexes, and radiation affecting time spent in the center in females only. Whole-brain analysis of cFos immunoreactivity in male mice indicated that amifostine and radiation altered regional connectivity in areas involved in novel object recognition. These data support that amifostine has potential as a countermeasure against cognitive injury following proton and heavy ion irradiation in males.
format	article
author	Sydney Weber Boutros Benjamin Zimmerman Benjamin Zimmerman Benjamin Zimmerman Sydney C. Nagy Joanne S. Lee Ruby Perez Jacob Raber Jacob Raber Jacob Raber
author_facet	Sydney Weber Boutros Benjamin Zimmerman Benjamin Zimmerman Benjamin Zimmerman Sydney C. Nagy Joanne S. Lee Ruby Perez Jacob Raber Jacob Raber Jacob Raber
author_sort	Sydney Weber Boutros
title	Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity
title_short	Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity
title_full	Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity
title_fullStr	Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity
title_full_unstemmed	Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity
title_sort	amifostine (wr-2721) mitigates cognitive injury induced by heavy ion radiation in male mice and alters behavior and brain connectivity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ab1d46c465bd4e8f8cb50b37ca5f511a
work_keys_str_mv	AT sydneyweberboutros amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT benjaminzimmerman amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT benjaminzimmerman amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT benjaminzimmerman amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT sydneycnagy amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT joanneslee amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT rubyperez amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT jacobraber amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT jacobraber amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity AT jacobraber amifostinewr2721mitigatescognitiveinjuryinducedbyheavyionradiationinmalemiceandaltersbehaviorandbrainconnectivity
_version_	1718426567146733568

Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity

Ejemplares similares