The effects of proton exposure on neurochemistry and behavior

Shukitt‐Hale, Barbara; Szprengiel, Aleksandra; Pluhar, J; Rabin, Bernard M.; Joseph, James A.

doi:10.1016/j.asr.2003.10.038

Cited by 42 publications

(22 citation statements)

References 17 publications

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“…One study measured male rats irradiated with a proton beam at 0, 1.5, 3, and 4 Gy and did not see any behavioral differences in spatial learning and memory at any dose [40]. This is in contrast to research on heavy atomic nuclei and high energy level particle (HZE) radiation.…”

Section: Discussionmentioning

confidence: 99%

Pomegranate Supplementation Improves Affective and Motor Behavior in Mice after Radiation Exposure

Dulcich

Hartman

2013

Evidence-Based Complementary and Alternative Medicine

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Currently, NASA has plans for extended space travel, and previous research indicates that space radiation can have negative effects on cognitive skills as well as physical and mental health. With long-term space travel, astronauts will be exposed to greater radiation levels. Research shows that an antioxidant-enriched diet may offer some protection against the cellular effects of radiation and may provide significant neuroprotection from the effects of radiation-induced cognitive and behavioral skill deficits. Ninety-six C57BL/6 mice (48 pomegranate fed and 48 control) were irradiated with proton radiation (2 Gy), and two-month postradiation behaviors were assessed using a battery of behavioral tests to measure cognitive and motor functions. Proton irradiation was associated with depression-like behaviors in the tail suspension test, but this effect was ameliorated by the pomegranate diet. Males, in general, displayed worse coordination and balance than females on the rotarod task, and the pomegranate diet ameliorated this effect. Overall, it appears that proton irradiation, which may be encountered in space, may induce a different pattern of behavioral deficits in males than females and that a pomegranate diet may confer protection against some of those effects.

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Section: Discussionmentioning

confidence: 99%

Pomegranate Supplementation Improves Affective and Motor Behavior in Mice after Radiation Exposure

Dulcich

Hartman

2013

Evidence-Based Complementary and Alternative Medicine

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“…Young-adult mice exposed to protons (3 and 4 Gy, 250 MeV) failed to show habituation to an open field when tested two weeks after exposure 28 . Similarly, spatial learning and memory in the water maze were not affected by proton irradiation of young-adult (250–275 g) rats (1.5, 3, or 4 Gy, 250 MeV) 29 . Whether habituation to an open field, object recognition, and spatial learning and memory in the water maze are sensitive to effects of proton irradiation in adult mice irradiated at 6 months of age, a biological age relevant to the typical ages of astronauts during space missions, is not known.…”

Section: Introductionmentioning

confidence: 90%

Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation

Impey

Jopson

Pelz

et al. 2017

Sci Rep

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The brain’s response to radiation exposure is an important concern for patients undergoing cancer therapy and astronauts on long missions in deep space. We assessed whether this response is specific and prolonged and is linked to epigenetic mechanisms. We focused on the response of the hippocampus at early (2-weeks) and late (20-week) time points following whole body proton irradiation. We examined two forms of DNA methylation, cytosine methylation (5mC) and hydroxymethylation (5hmC). Impairments in object recognition, spatial memory retention, and network stability following proton irradiation were observed at the two-week time point and correlated with altered gene expression and 5hmC profiles that mapped to specific gene ontology pathways. Significant overlap was observed between DNA methylation changes at the 2 and 20-week time points demonstrating specificity and retention of changes in response to radiation. Moreover, a novel class of DNA methylation change was observed following an environmental challenge (i.e. space irradiation), characterized by both increased and decreased 5hmC levels along the entire gene body. These changes were mapped to genes encoding neuronal functions including postsynaptic gene ontology categories. Thus, the brain’s response to proton irradiation is both specific and prolonged and involves novel remodeling of non-random regions of the epigenome.

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“…Shukitt-Hale et al (2) showed that rats exposed to proton radiation doses of 1.5, 3 and 4 Gy did not differ from the control group 1.5 months after irradiation. As a result, the authors suggested that proton radiation may not be as deleterious as HZE particles.…”

mentioning

confidence: 98%

A Single Low Dose of Proton Radiation Induces Long-Term Behavioral and Electrophysiological Changes in Mice

Bellone¹,

Rudobeck

Hartman³

et al. 2015

Radiation Research

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Astronauts traveling outside Earth's magnetosphere risk exposure to charged particle radiation that may cause neurophysiological changes and behavioral deficits. Although proton particles comprise a large portion of the space radiation environment, little has been published on the effects of low-dose proton radiation on central nervous system function. In the current study, we irradiated young male mice with 0.5 Gy 150 MeV protons and assessed the effects on behavior and hippocampal neurophysiology. Spatial learning ability, a sensitive behavioral marker of hippocampal damage, was assessed using the water maze and Barnes maze before irradiation and repeatedly 3 and 6 months after irradiation. Evoked field excitatory postsynaptic potentials (fEPSPs) and population spikes, long-term potentiation (LTP) and spontaneous oscillations (SOs) triggered by incubation with Mg(2+)-free media (reflecting interictal epileptiform activity) were assessed 9 months after irradiation in vitro in hippocampal slice preparations. Irradiated mice exhibited impaired reversal learning in the water maze compared to control mice 6 months after irradiation. Proton radiation did not affect LTP, but significantly increased fEPSP slopes and reduced the incidence of SOs 9 months after irradiation. These findings suggest that a single exposure to low-dose proton radiation can increase synaptic excitability and suppress the propensity for epileptiform activity. Such findings of functional alterations in the irradiated mouse hippocampus have implications for extended manned space missions planned in the near future.

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The effects of proton exposure on neurochemistry and behavior

Cited by 42 publications

References 17 publications

Pomegranate Supplementation Improves Affective and Motor Behavior in Mice after Radiation Exposure

Pomegranate Supplementation Improves Affective and Motor Behavior in Mice after Radiation Exposure

Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation

A Single Low Dose of Proton Radiation Induces Long-Term Behavioral and Electrophysiological Changes in Mice

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