Postsynaptic density radiation signature following space irradiation

Soren Impey; Carl Pelz; Lara-Kirstie Riparip; Amanuel Tafessu; Fatema Fareh; Damian G Zuloaga; Tessa Marzulla; Blair Stewart; Susanna Rosi; Mitchell S Turker; Jacob Raber

doi:10.3389/fphys.2023.1215535

Postsynaptic density radiation signature following space irradiation

Front Physiol. 2023 Jun 27:14:1215535. doi: 10.3389/fphys.2023.1215535. eCollection 2023.

Authors

Soren Impey^{1

2}, Carl Pelz¹, Lara-Kirstie Riparip³, Amanuel Tafessu¹, Fatema Fareh¹, Damian G Zuloaga⁴, Tessa Marzulla⁴, Blair Stewart⁴, Susanna Rosi³, Mitchell S Turker⁵, Jacob Raber^{4

6}

Affiliations

¹ Department of Pediatrics, Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR, United States.
² Dow Neuroscience Laboratories, Department of Cell and Developmental Biology, Legacy Research Institute, Legacy Health Systems, Oregon Health and Science University, Portland, OR, United States.
³ Departments of Neurological Surgery and Physical Therapy and Rehabilitation Science, Brain and Spinal Injury Center, University of California, San Francisco, San Francisco, CA, United States.
⁴ Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States.
⁵ Department of Molecular and Medical Genetics, Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, United States.
⁶ Departments of Neurology and Radiation Medicine, Division of Neuroscience ONPRC, Oregon Health and Science University, Portland, OR, United States.

Abstract

Introduction: The response of the brain to space radiation is an important concern for astronauts during space missions. Therefore, we assessed the response of the brain to ²⁸Si ion irradiation (600 MeV/n), a heavy ion present in the space environment, on cognitive performance and whether the response is associated with altered DNA methylation in the hippocampus, a brain area important for cognitive performance. Methods: We determined the effects of ²⁸Si ion irradiation on object recognition, 6-month-old mice irradiated with ²⁸Si ions (600 MeV/n, 0.3, 0.6, and 0.9 Gy) and cognitively tested two weeks later. In addition, we determined if those effects were associated with alterations in hippocampal networks and/or hippocampal DNA methylation. Results: At 0.3 Gy, but not at 0.6 Gy or 0.9 Gy, ²⁸Si ion irradiation impaired cognition that correlated with altered gene expression and 5 hmC profiles that mapped to specific gene ontology pathways. Comparing hippocampal DNA hydroxymethylation following proton, ⁵⁶Fe ion, and ²⁸Si ion irradiation revealed a general space radiation synaptic signature with 45 genes that are associated with profound phenotypes. The most significant categories were glutamatergic synapse and postsynaptic density. Discussion: The brain's response to space irradiation involves novel excitatory synapse and postsynaptic remodeling.

Keywords: DNA methylation; hippocampus; object recognition; postsynaptic; space radiation.

Grants and funding

This work was supported by NASA grants NNJ12ZSA001N, 80NSSC19K0498–P00001, NIDA T32DA007262, the Legacy Good Samaritan Foundation, and the development accounts of JR and SI.