Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects

Abstract Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rat...

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Autores principales:	Michael T. Williams, Chiho Sugimoto, Samantha L. Regan, Emily M. Pitzer, Adam L. Fritz, Anthony E. Mascia, Mathieu Sertorio, Ralph E. Vatner, John P. Perentesis, Charles V. Vorhees
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d32edd717014b9596a855396e69d6d1
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spelling	oai:doaj.org-article:5d32edd717014b9596a855396e69d6d12021-12-02T16:18:05ZWhole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects10.1038/s41598-020-78128-12045-2322https://doaj.org/article/5d32edd717014b9596a855396e69d6d12020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78128-1https://doaj.org/toc/2045-2322Abstract Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rats (10/group) received a single dose of 0, 11, 14, 17, or 20 Gy irradiation (the 20 Gy group was not used because 50% died). Rats were tested once/week for 5 weeks post-irradiation for activity, coordination, and startle. Cognitive assessment began 6-weeks post-irradiation with novel object recognition (NOR), egocentric learning, allocentric learning, reference memory, and proximal cue learning. Proton exposure had the largest effect on activity and prepulse inhibition of startle 1-week post-irradiation that dissipated each week. 6-weeks post-irradiation, there were no effects on NOR, however proton exposure impaired egocentric (Cincinnati water maze) and allocentric learning and caused reference memory deficits (Morris water maze), but did not affect proximal cue learning or swimming performance. Proton groups also had reduced striatal levels of the dopamine transporter, tyrosine hydroxylase, and the dopamine receptor D1, effects consistent with egocentric learning deficits. This new model will facilitate investigations of different proton dose rates and drugs to ameliorate the cognitive sequelae of proton radiotherapy.Michael T. WilliamsChiho SugimotoSamantha L. ReganEmily M. PitzerAdam L. FritzAnthony E. MasciaMathieu SertorioRalph E. VatnerJohn P. PerentesisCharles V. VorheesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-20 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael T. Williams Chiho Sugimoto Samantha L. Regan Emily M. Pitzer Adam L. Fritz Anthony E. Mascia Mathieu Sertorio Ralph E. Vatner John P. Perentesis Charles V. Vorhees Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects
description	Abstract Proton radiotherapy causes less off-target effects than X-rays but is not without effect. To reduce adverse effects of proton radiotherapy, a model of cognitive deficits from conventional proton exposure is needed. We developed a model emphasizing multiple cognitive outcomes. Adult male rats (10/group) received a single dose of 0, 11, 14, 17, or 20 Gy irradiation (the 20 Gy group was not used because 50% died). Rats were tested once/week for 5 weeks post-irradiation for activity, coordination, and startle. Cognitive assessment began 6-weeks post-irradiation with novel object recognition (NOR), egocentric learning, allocentric learning, reference memory, and proximal cue learning. Proton exposure had the largest effect on activity and prepulse inhibition of startle 1-week post-irradiation that dissipated each week. 6-weeks post-irradiation, there were no effects on NOR, however proton exposure impaired egocentric (Cincinnati water maze) and allocentric learning and caused reference memory deficits (Morris water maze), but did not affect proximal cue learning or swimming performance. Proton groups also had reduced striatal levels of the dopamine transporter, tyrosine hydroxylase, and the dopamine receptor D1, effects consistent with egocentric learning deficits. This new model will facilitate investigations of different proton dose rates and drugs to ameliorate the cognitive sequelae of proton radiotherapy.
format	article
author	Michael T. Williams Chiho Sugimoto Samantha L. Regan Emily M. Pitzer Adam L. Fritz Anthony E. Mascia Mathieu Sertorio Ralph E. Vatner John P. Perentesis Charles V. Vorhees
author_facet	Michael T. Williams Chiho Sugimoto Samantha L. Regan Emily M. Pitzer Adam L. Fritz Anthony E. Mascia Mathieu Sertorio Ralph E. Vatner John P. Perentesis Charles V. Vorhees
author_sort	Michael T. Williams
title	Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects
title_short	Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects
title_full	Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects
title_fullStr	Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects
title_full_unstemmed	Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects
title_sort	whole brain proton irradiation in adult sprague dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5d32edd717014b9596a855396e69d6d1
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Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects

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