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01-03-2015 | Original Article

Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation

Authors: Vipan K. Parihar, Junaid Pasha, Katherine K. Tran, Brianna M. Craver, Munjal M. Acharya, Charles L. Limoli

Published in: Brain Structure and Function | Issue 2/2015

Abstract

Cranial radiotherapy is used routinely to control the growth of primary and secondary brain tumors, but often results in serious and debilitating cognitive dysfunction. In part due to the beneficial dose depth distributions that may spare normal tissue damage, the use of protons to treat CNS and other tumor types is rapidly gaining popularity. Astronauts exposed to lower doses of protons in the space radiation environment are also at risk for developing adverse CNS complications. To explore the consequences of whole body proton irradiation, mice were subjected to 0.1 and 1 Gy and analyzed for morphometric changes in hippocampal neurons 10 and 30 days following exposure. Significant dose-dependent reductions (~33 %) in dendritic complexity were found, when dendritic length, branching and area were analyzed 30 days after exposure. At equivalent doses and times, significant reductions in the number (~30 %) and density (50–75 %) of dendritic spines along hippocampal neurons of the dentate gyrus were also observed. Immature spines (filopodia, long) exhibited the greatest sensitivity (1.5- to 3-fold) to irradiation, while more mature spines (mushroom) were more resistant to changes over a 1-month post-irradiation timeframe. Irradiated granule cell neurons spanning the subfields of the dentate gyrus showed significant and dose-responsive reductions in synaptophysin expression, while the expression of postsynaptic density protein (PSD-95) was increased significantly. These findings corroborate our past work using photon irradiation, and demonstrate for the first time, dose-responsive changes in dendritic complexity, spine density and morphology and synaptic protein levels following exposure to low-dose whole body proton irradiation.

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Title: Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation
Authors: Vipan K. Parihar
Junaid Pasha
Katherine K. Tran
Brianna M. Craver
Munjal M. Acharya
Charles L. Limoli
Publication date: 01-03-2015
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 2/2015
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-014-0709-9

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Persistent changes in neuronal structure and synaptic plasticity caused by proton irradiation

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