Radiation induces acute alterations in neuronal function.

Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation...

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Autores principales:	Peter H Wu, Steven Coultrap, Chelsea Pinnix, Kurtis D Davies, Ramesh Tailor, Kian K Ang, Michael D Browning, David R Grosshans
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1fbe0b5fdb174c2db1567c85f60d0b06
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spelling	oai:doaj.org-article:1fbe0b5fdb174c2db1567c85f60d0b062021-11-18T07:17:21ZRadiation induces acute alterations in neuronal function.1932-620310.1371/journal.pone.0037677https://doaj.org/article/1fbe0b5fdb174c2db1567c85f60d0b062012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22662188/?tool=EBIhttps://doaj.org/toc/1932-6203Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(A)Rs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.Peter H WuSteven CoultrapChelsea PinnixKurtis D DaviesRamesh TailorKian K AngMichael D BrowningDavid R GrosshansPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37677 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peter H Wu Steven Coultrap Chelsea Pinnix Kurtis D Davies Ramesh Tailor Kian K Ang Michael D Browning David R Grosshans Radiation induces acute alterations in neuronal function.
description	Every year, nearly 200,000 patients undergo radiation for brain tumors. For both patients and caregivers the most distressing adverse effect is impaired cognition. Efforts to protect against this debilitating effect have suffered from inadequate understanding of the cellular mechanisms of radiation damage. In the past it was accepted that radiation-induced normal tissue injury resulted from a progressive reduction in the survival of clonogenic cells. Moreover, because radiation-induced brain dysfunction is believed to evolve over months to years, most studies have focused on late changes in brain parenchyma. However, clinically, acute changes in cognition are also observed. Because neurons are fully differentiated post-mitotic cells, little information exists on the acute effects of radiation on synaptic function. The purpose of our study was to assess the potential acute effects of radiation on neuronal function utilizing ex vivo hippocampal brain slices. The cellular localization and functional status of excitatory and inhibitory neurotransmitter receptors was identified by immunoblotting. Electrophysiological recordings were obtained both for populations of neuronal cells and individual neurons. In the dentate gyrus region of isolated ex vivo slices, radiation led to early decreases in tyrosine phosphorylation and removal of excitatory N-methyl-D-aspartate receptors (NMDARs) from the cell surface while simultaneously increasing the surface expression of inhibitory gamma-aminobutyric acid receptors (GABA(A)Rs). These alterations in cellular localization corresponded with altered synaptic responses and inhibition of long-term potentiation. The non-competitive NMDAR antagonist memantine blocked these radiation-induced alterations in cellular distribution. These findings demonstrate acute effects of radiation on neuronal cells within isolated brain slices and open new avenues for study.
format	article
author	Peter H Wu Steven Coultrap Chelsea Pinnix Kurtis D Davies Ramesh Tailor Kian K Ang Michael D Browning David R Grosshans
author_facet	Peter H Wu Steven Coultrap Chelsea Pinnix Kurtis D Davies Ramesh Tailor Kian K Ang Michael D Browning David R Grosshans
author_sort	Peter H Wu
title	Radiation induces acute alterations in neuronal function.
title_short	Radiation induces acute alterations in neuronal function.
title_full	Radiation induces acute alterations in neuronal function.
title_fullStr	Radiation induces acute alterations in neuronal function.
title_full_unstemmed	Radiation induces acute alterations in neuronal function.
title_sort	radiation induces acute alterations in neuronal function.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/1fbe0b5fdb174c2db1567c85f60d0b06
work_keys_str_mv	AT peterhwu radiationinducesacutealterationsinneuronalfunction AT stevencoultrap radiationinducesacutealterationsinneuronalfunction AT chelseapinnix radiationinducesacutealterationsinneuronalfunction AT kurtisddavies radiationinducesacutealterationsinneuronalfunction AT rameshtailor radiationinducesacutealterationsinneuronalfunction AT kiankang radiationinducesacutealterationsinneuronalfunction AT michaeldbrowning radiationinducesacutealterationsinneuronalfunction AT davidrgrosshans radiationinducesacutealterationsinneuronalfunction
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Radiation induces acute alterations in neuronal function.

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