Low (60 cGy) Doses of Fe-56 HZE-Particle Radiation Lead to a Persistent Reduction in the Glutamatergic Readily Releasable Pool in Rat Hippocampal Synaptosomes
ABSTRACT Exposure to galactic cosmic radiation (GCR) is considered to be a potential health risk in long-term space travel, and it represents a significant risk to the central nervous system (CNS). The most harmful component of GCR is the HZE [high-mass, highly charged (Z), high-energy] particles, e.g. (56)Fe. In ground-based experiments, exposure to HZE-particle radiation induces pronounced deficits in hippocampus-dependent learning and memory in rodents. The mechanisms underlying these impairments are mostly unknown, but some studies suggest that HZE-particle exposure perturbs the regulation of long-term potentiation (LTP) at the CA1 synapse in the hippocampus. In this study, we irradiated rats with 60 cGy of 1 GeV (56)Fe-particle radiation and established its impact on hippocampal glutamatergic neurotransmissions at 3 and 6 months after exposure. Exposure to 60 cGy (56)Fe-particle radiation significantly (P < 0.05) reduced hyperosmotic sucrose evoked [(3)H]-glutamate release from hippocampal synaptosomes, a measure of the readily releasable vesicular pool (RRP). This HZE-particle-induced reduction in the glutamatergic RRP persisted for at least 6 months after exposure. At 90 days postirradiation, there was a significant reduction in the expression of the NR1, NR2A and NR2B subunits of the glutamatergic NMDA receptor. The level of the NR2A protein remained suppressed at 180 days postirradiation, but the level of NR2B and NR1 proteins returned to or exceeded normal levels, respectively. Overall, this study shows that hippocampal glutamatergic transmission is sensitive to relative low doses of (56)Fe particles. Whether the observed HZE-particle-induced change in glutamate transmission, which plays a critical role in learning and memory, is the cause of HZE-particle-induced neurocognitive impairment requires further investigation.
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ABSTRACT: The concept of radiation risk for piloted interplanetary flights is proposed and substantiated. Heavy charged particles arriving among galactic cosmic rays (GCR) have powerful damaging actions when they pass through biological structures. This results from the local deposition of large amounts of energy in the tracks of heavy charged particles. Heavy ions have high biological effectiveness in relation to the genetic structures of cells, as well as at the whole-body level, including actions of brain structures. The most radiation-sensitive area of the central nervous system, particularly to the actions of heavy charged particles, is the hippocampus. Animals irradiated with accelerated iron ions at doses corresponding to the actual fluxes of heavy GCR particles to which crews would be exposed on a Mars mission develop severe impairment of behavioral functions during the post-irradiation period. The radiation risk to crews in interplanetary flights is assessed using the concept of “successful mission outcome probability.” The critical target for heavy nuclei in GCR in these conditions may consist of central nervous system structures, damage to which may lead to modification of the higher integrative functions of the brain, leading to degradation of cosmonaut performance.Neuroscience and Behavioral Physiology 12/2014; 45(1). DOI:10.1007/s11055-014-0044-x
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ABSTRACT: The evaluation of potential health risks associated with neuronal exposure to space radiation is critical for future long duration space travel. The purpose of this study was to evaluate and compare the effects of low-dose proton and high-energy charged particle (HZE) radiation on electrophysiological parameters of the granule cells in the dentate gyrus (DG) of the hippocampus and its associated functional consequences. We examined excitatory and inhibitory neurotransmission in DG granule cells (DGCs) in dorsal hippocampal slices from male C57BL/6 mice at 3 months after whole body irradiation with accelerated proton, silicon or iron particles. Multielectrode arrays were used to investigate evoked field synaptic potentials, an extracellular measurement of synaptic excitability in the perforant path to DG synaptic pathway. Whole-cell patch clamp recordings were used to measure miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in DGCs. Exposure to proton radiation increased synaptic excitability and produced dose-dependent decreases in amplitude and charge transfer of mIPSCs, without affecting the expression of γ-aminobutyric acid type A receptor α2, β3 and γ2 subunits determined by Western blotting. Exposure to silicon radiation had no significant effects on synaptic excitability, mEPSCs or mIPSCs of DGCs. Exposure to iron radiation had no effect on synaptic excitability and mIPSCs, but significantly increased mEPSC frequency at 1 Gy, without changes in mEPSC kinetics, suggesting a presynaptic mechanism. Overall, the data suggest that proton and HZE exposure results in radiation dose- and species-dependent long-lasting alterations in synaptic neurotransmission, which could cause radiation-induced impairment of hippocampal-dependent cognitive functions.Radiation Research 11/2014; 182(6). DOI:10.1667/RR13647.1 · 2.45 Impact Factor
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ABSTRACT: Ionizing radiation induces altered brain tissue homeostasis and can lead to morphological and functional deficits. In this study, adult male Wistar rats received whole-body exposure with fractionated doses of gamma rays (a total dose of 5 Gy) and were investigated 30 and 60 days later. Immunohistochemistry and confocal microscopy were used to determine proliferation rate of cells residing or derived from the forebrain anterior subventricular zone (SVZa) and microglia distributed along and/or adjacent to subventricular zone-olfactory bulb axis. Cell counting was performed in four anatomical parts along the well-defined pathway, known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. Different spatiotemporal distribution pattern of cell proliferation was seen up to 60 days after irradiation through the migratory pathway. A population of neuroblasts underwent less evident changes up to 60 days after treatment. Fractionated exposure led to decline or loss of resting as well as reactive forms of microglia until 60 days after irradiation. Results showed that altered expression of the SVZa derived cells and ultimative decrease of microglia may contribute to development of radiation-induced late effects.Neurochemical Research 12/2014; 40(3). DOI:10.1007/s11064-014-1495-8 · 2.55 Impact Factor