Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response

Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decl...

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Autores principales:	Francesca Antonelli, Arianna Casciati, Montserrat Belles, Noemi Serra, Maria Victoria Linares-Vidal, Carmela Marino, Mariateresa Mancuso, Simonetta Pazzaglia
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ionizing radiation astrocytes hippocampal neurogenesis cognitive effects Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1d88959298c34f2998b92266681b9404
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spelling	oai:doaj.org-article:1d88959298c34f2998b92266681b94042021-11-25T17:58:15ZLong-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response10.3390/ijms2222126051422-00671661-6596https://doaj.org/article/1d88959298c34f2998b92266681b94042021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12605https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies. Based on recent evidence, showing that manipulation of the Shh pathway carries therapeutic potential for brain repair and functional recovery after injury, here we evaluate how radiation-induced hippocampal alterations are modulated by the constitutive activation of the Shh signaling pathway in Patched 1 heterozygous mice (<i>Ptch1</i><sup>+/−</sup>). Our results show, for the first time, an overall protective effect of constitutive Shh pathway activation on hippocampal radiation injury. This activation, through modulation of the proneural gene network, leads to a long-term reduction of hippocampal deficits in the stem cell and new neuron compartments and to the mitigation of radio-induced astrogliosis, despite some behavioral alterations still being detected in <i>Ptch1</i><sup>+/−</sup> mice. A better understanding of the pathogenic mechanisms responsible for the neural decline following irradiation is essential for identifying prevention measures to contain the harmful consequences of irradiation. Our data have important translational implications as they suggest a role for Shh pathway manipulation to provide the therapeutic possibility of improving brain repair and functional recovery after radio-induced injury.Francesca AntonelliArianna CasciatiMontserrat BellesNoemi SerraMaria Victoria Linares-VidalCarmela MarinoMariateresa MancusoSimonetta PazzagliaMDPI AGarticleionizing radiationastrocyteshippocampal neurogenesiscognitive effectsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12605, p 12605 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ionizing radiation astrocytes hippocampal neurogenesis cognitive effects Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ionizing radiation astrocytes hippocampal neurogenesis cognitive effects Biology (General) QH301-705.5 Chemistry QD1-999 Francesca Antonelli Arianna Casciati Montserrat Belles Noemi Serra Maria Victoria Linares-Vidal Carmela Marino Mariateresa Mancuso Simonetta Pazzaglia Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response
description	Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies. Based on recent evidence, showing that manipulation of the Shh pathway carries therapeutic potential for brain repair and functional recovery after injury, here we evaluate how radiation-induced hippocampal alterations are modulated by the constitutive activation of the Shh signaling pathway in Patched 1 heterozygous mice (<i>Ptch1</i><sup>+/−</sup>). Our results show, for the first time, an overall protective effect of constitutive Shh pathway activation on hippocampal radiation injury. This activation, through modulation of the proneural gene network, leads to a long-term reduction of hippocampal deficits in the stem cell and new neuron compartments and to the mitigation of radio-induced astrogliosis, despite some behavioral alterations still being detected in <i>Ptch1</i><sup>+/−</sup> mice. A better understanding of the pathogenic mechanisms responsible for the neural decline following irradiation is essential for identifying prevention measures to contain the harmful consequences of irradiation. Our data have important translational implications as they suggest a role for Shh pathway manipulation to provide the therapeutic possibility of improving brain repair and functional recovery after radio-induced injury.
format	article
author	Francesca Antonelli Arianna Casciati Montserrat Belles Noemi Serra Maria Victoria Linares-Vidal Carmela Marino Mariateresa Mancuso Simonetta Pazzaglia
author_facet	Francesca Antonelli Arianna Casciati Montserrat Belles Noemi Serra Maria Victoria Linares-Vidal Carmela Marino Mariateresa Mancuso Simonetta Pazzaglia
author_sort	Francesca Antonelli
title	Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response
title_short	Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response
title_full	Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response
title_fullStr	Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response
title_full_unstemmed	Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response
title_sort	long-term effects of ionizing radiation on the hippocampus: linking effects of the sonic hedgehog pathway activation with radiation response
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1d88959298c34f2998b92266681b9404
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Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response

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