Short- and long-term effects of 56Fe irradiation on cognition and hippocampal DNA methylation and gene expression

Soren Impey, Timothy Jopson, Carl Pelz, Amanuel Tafessu, Fatema Fareh, Damian Zuloaga, Tessa Marzulla, Lara Kirstie Riparip, Blair Stewart, Susanna Rosi, Mitchell Turker, Jacob Raber

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Astronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. We showed previously that object recognition requiring the hippocampus, a structure critical for cognitive function, is affected in 2-month-old mice irradiated with 56Fe ions. Here we examined object recognition in 6-month-old mice irradiated with 56Fe ions, a biological age more relevant to the typical ages of astronauts. Moreover, because the mechanisms mediating the detrimental effects of 56Fe ions on hippocampal function are unclear, we examined changes in hippocampal networks involved in synaptic plasticity and memory, gene expression, and epigenetic changes in cytosine methylation (5mC) and hydroxymethylation (5hmC) that could accompany changes in gene expression. We assessed the effects of whole body 56Fe ion irradiation at early (2 weeks) and late (20 weeks) time points on hippocampus-dependent memory and hippocampal network stability, and whether these effects are associated with epigenetic changes in hippocampal DNA methylation (both 5mC and 5hmC) and gene expression. Results: At the two-week time point, object recognition and network stability were impaired following irradiation at the 0.1 and 0.4 Gy dose, but not following irradiation at the 0.2 Gy dose. No impairments in object recognition or network stability were seen at the 20-week time point at any irradiation dose used. Consistent with this pattern, the significance of pathways for gene categories for 5hmC was lower, though not eliminated, at the 20-week time point compared to the 2-week time point. Similarly, significant changes were observed for 5mC gene pathways at the 2-week time point, but no significant gene categories were observed at the 20-week time point. Only the 5hmC changes tracked with gene expression changes. Conclusions: Dose- and time-dependent epigenomic remodeling in the hippocampus following 56Fe ion exposure correlates with behavioral changes.

Original languageEnglish (US)
Article number825
JournalBMC Genomics
Volume17
Issue number1
DOIs
StatePublished - Oct 24 2016

Fingerprint

DNA Methylation
Cognition
Gene Expression
Ions
Epigenomics
Astronauts
Hippocampus
Genes
Neuronal Plasticity
Cytosine
Methylation
Recognition (Psychology)
Health

Keywords

  • Cognition
  • DNA methylation
  • Gene expression
  • Hippocampus
  • Network stability

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Short- and long-term effects of 56Fe irradiation on cognition and hippocampal DNA methylation and gene expression. / Impey, Soren; Jopson, Timothy; Pelz, Carl; Tafessu, Amanuel; Fareh, Fatema; Zuloaga, Damian; Marzulla, Tessa; Riparip, Lara Kirstie; Stewart, Blair; Rosi, Susanna; Turker, Mitchell; Raber, Jacob.

In: BMC Genomics, Vol. 17, No. 1, 825, 24.10.2016.

Research output: Contribution to journalArticle

Impey, S, Jopson, T, Pelz, C, Tafessu, A, Fareh, F, Zuloaga, D, Marzulla, T, Riparip, LK, Stewart, B, Rosi, S, Turker, M & Raber, J 2016, 'Short- and long-term effects of 56Fe irradiation on cognition and hippocampal DNA methylation and gene expression', BMC Genomics, vol. 17, no. 1, 825. https://doi.org/10.1186/s12864-016-3110-7
Impey, Soren ; Jopson, Timothy ; Pelz, Carl ; Tafessu, Amanuel ; Fareh, Fatema ; Zuloaga, Damian ; Marzulla, Tessa ; Riparip, Lara Kirstie ; Stewart, Blair ; Rosi, Susanna ; Turker, Mitchell ; Raber, Jacob. / Short- and long-term effects of 56Fe irradiation on cognition and hippocampal DNA methylation and gene expression. In: BMC Genomics. 2016 ; Vol. 17, No. 1.
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AU - Fareh, Fatema

AU - Zuloaga, Damian

AU - Marzulla, Tessa

AU - Riparip, Lara Kirstie

AU - Stewart, Blair

AU - Rosi, Susanna

AU - Turker, Mitchell

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AB - Background: Astronauts are exposed to 56Fe ions that may pose a significant health hazard during and following prolonged missions in deep space. We showed previously that object recognition requiring the hippocampus, a structure critical for cognitive function, is affected in 2-month-old mice irradiated with 56Fe ions. Here we examined object recognition in 6-month-old mice irradiated with 56Fe ions, a biological age more relevant to the typical ages of astronauts. Moreover, because the mechanisms mediating the detrimental effects of 56Fe ions on hippocampal function are unclear, we examined changes in hippocampal networks involved in synaptic plasticity and memory, gene expression, and epigenetic changes in cytosine methylation (5mC) and hydroxymethylation (5hmC) that could accompany changes in gene expression. We assessed the effects of whole body 56Fe ion irradiation at early (2 weeks) and late (20 weeks) time points on hippocampus-dependent memory and hippocampal network stability, and whether these effects are associated with epigenetic changes in hippocampal DNA methylation (both 5mC and 5hmC) and gene expression. Results: At the two-week time point, object recognition and network stability were impaired following irradiation at the 0.1 and 0.4 Gy dose, but not following irradiation at the 0.2 Gy dose. No impairments in object recognition or network stability were seen at the 20-week time point at any irradiation dose used. Consistent with this pattern, the significance of pathways for gene categories for 5hmC was lower, though not eliminated, at the 20-week time point compared to the 2-week time point. Similarly, significant changes were observed for 5mC gene pathways at the 2-week time point, but no significant gene categories were observed at the 20-week time point. Only the 5hmC changes tracked with gene expression changes. Conclusions: Dose- and time-dependent epigenomic remodeling in the hippocampus following 56Fe ion exposure correlates with behavioral changes.

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KW - Network stability

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