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

Vipan K Parihar1, Junaid Pasha, Katherine K Tran

  • 1Department of Radiation Oncology, University of California, Medical Sciences I, Room B-146B, Irvine, CA, 92697-2695, USA.

Brain Structure & Function
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Summary

Low-dose proton irradiation damages hippocampal neurons in mice, affecting dendritic complexity and spine density. These changes in brain cells are dose-dependent and impact synaptic protein levels, highlighting potential risks from proton therapy and space radiation.

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Area of Science:

  • Neuroscience
  • Radiation Biology
  • Oncology

Background:

  • Cranial radiotherapy, including proton therapy, is used for brain tumors but can cause cognitive dysfunction.
  • Proton irradiation is increasingly used due to favorable dose distributions, sparing normal tissues.
  • Astronauts face risks from space proton radiation, potentially leading to central nervous system (CNS) complications.

Purpose of the Study:

  • To investigate the effects of low-dose whole-body proton irradiation on hippocampal neurons in mice.
  • To analyze dose-dependent morphometric changes in neurons and synaptic proteins following proton exposure.

Main Methods:

  • Mice were exposed to 0.1 and 1 Gy of whole-body proton irradiation.
  • Hippocampal neurons were analyzed 10 and 30 days post-irradiation for dendritic complexity and spine density.
  • Synaptophysin and PSD-95 protein expression levels were quantified in irradiated neurons.

Main Results:

  • Significant dose-dependent reductions in dendritic complexity (length, branching, area) were observed 30 days post-irradiation.
  • A dose-responsive decrease in the number and density of dendritic spines was noted, with immature spines being more sensitive.
  • Irradiated neurons showed reduced synaptophysin and increased PSD-95 expression, indicating altered synaptic function.

Conclusions:

  • Low-dose proton irradiation induces significant, dose-dependent structural and molecular changes in hippocampal neurons.
  • These findings suggest potential risks associated with proton therapy and space radiation exposure to the CNS.
  • The study highlights the sensitivity of neuronal morphology and synaptic proteins to proton irradiation.