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

Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA.
Radiation Research (Impact Factor: 2.91). 11/2010; 174(5):618-23. DOI: 10.1667/RR1988.1
Source: PubMed


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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    • " 2010 ; Cherry et al . , 2012 ; Shukitt - Hale et al . , 2013 ) . A relatively low dose at 50 cGy was shown to induce hippo - campal neurogenesis and neuroinflammation in mice ( Rola et al . , 2008 ) ; a low dose at 60 cGy was found to lead to a persistent reduction in the glutamatergic readily releasable pool of hippocampal synaptosomes in rats ( Machida et al . , 2010 ) , and an even lower dose at 20 cGy was reported to cause a persistent reduction in spatial learning ability in rats ( Britten et al . , 2012 ) . Probably as a result of the higher LET of Fe particles , the survival prob - ability of the cells hit by the Fe particles would be fairly small . Thus loss of critical cellular components in "
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    • "Studies have demonstrated radiationinduced changes in hippocampal cellular activity (Gangloff and Haley, 1960; Bassant and Court, 1978), synaptic efficiency/spike generation (Bassant and Court, 1978; Pellmar and Lepinski, 1993), and neuronal gene expression (Noel et al., 1998; Rosi et al., 2008). For example, irradiating the rodent brain with single and fractionated doses produces changes in (i) neuronal receptor expression of the immediate-early gene activity-regulated cytoskeleton-associated protein (Arc) (Rosi et al., 2008), (ii) N methyl-D-aspartic acid (NMDA) receptor subunits (Shi et al., 2006; Machida et al., 2010), (iii) glutaminergic transmission (Rohde et al., 1979; Machida et al., 2010), and (iv) hippocampal long-term potentiation (LTP; Snyder et al., 2001; Vlkolinsky et al., 2008); all are important for synaptic plasticity and cognition. "
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