Radiation-induced alterations in synaptic neurotransmission of dentate granule cells depend on the dose and species of charged particles.

Radiation-induced alterations in synaptic neurotransmission of dentate granule cells depend on the dose and species of charged particles.

Radiation research (2014-11-18)

V N Marty, R Vlkolinsky, N Minassian, T Cohen, G A Nelson, I Spigelman

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.

MATERIALS

Product Number

Brand

Product Description

209309

Sigma-Aldrich

Iron, powder, −325 mesh, 97%

IRMM524B

Iron, IRMM^®, certified reference material, 0.5 mm wire

267945

Sigma-Aldrich

Iron, chips, 99.98% trace metals basis

356808

Sigma-Aldrich

Iron, foil, thickness 0.1 mm, ≥99.9% trace metals basis

A2129

Sigma-Aldrich

γ-Aminobutyric acid, ≥99%

A5835

Sigma-Aldrich

γ-Aminobutyric acid, BioXtra, ≥99%

44890

Sigma-Aldrich

Iron, puriss. p.a., carbonyl-Iron powder, low in magnesium and manganese compounds, ≥99.5% (RT)

GF63891726

Iron, insulated wire, 10m, conductor diameter 0.25mm, insulation thickness 0.01mm, polyester insulation

03835

Supelco

γ-Aminobutyric acid, analytical standard

Y0001404

Vigabatrin impurity D, European Pharmacopoeia (EP) Reference Standard

GF40975601

Iron, tube, 500mm, outside diameter 3.18mm, inside diameter 1.96mm, wall thickness 0.61mm, as drawn, 99.5%

GF06733818

Iron, tube, 200mm, outside diameter 5.0mm, inside diameter 4.5mm, wall thickness 0.25mm, as drawn, 99.5%

GF67418062

Iron, tube, 500mm, outside diameter 12.0mm, inside diameter 9mm, wall thickness 1.5mm, annealed, 99.5%

GF21950197

Iron, tube, 1000mm, outside diameter 3.18mm, inside diameter 1.96mm, wall thickness 0.61mm, as drawn, 99.5%

GF28189525

Iron, tube, 200mm, outside diameter 12.7mm, inside diameter 9.5mm, wall thickness 1.6mm, annealed, 99.5%

GF55674164

Iron, tube, 1000mm, outside diameter 5.0mm, inside diameter 4.5mm, wall thickness 0.25mm, as drawn, 99.5%

GF18645240

Iron, tube, 100mm, outside diameter 10.0mm, inside diameter 7mm, wall thickness 1.5mm, annealed, 99.5%

GF37941240

Iron, tube, 1000mm, outside diameter 2.30mm, inside diameter 2.07mm, wall thickness 0.115mm, as drawn, 99.5%

GF92236428

Iron, tube, 500mm, outside diameter 12.7mm, inside diameter 9.5mm, wall thickness 1.6mm, annealed, 99.5%

GF93209328

Iron, tube, 200mm, outside diameter 8.0mm, inside diameter 5mm, wall thickness 1.5mm, annealed, 99.5%

GF08932934

Iron, tube, 500mm, outside diameter 15.0mm, inside diameter 12mm, wall thickness 1.5mm, annealed, 99.5%

GF45478604

Iron, tube, 200mm, outside diameter 6.35mm, inside diameter 5.35mm, wall thickness 0.5mm, as drawn, 99.8%

GF83953952

Iron, tube, 200mm, outside diameter 2.38mm, inside diameter 1.6mm, wall thickness 0.39mm, as drawn, 99.8+%

GF35765826

Iron, tube, 100mm, outside diameter 3.18mm, inside diameter 1.96mm, wall thickness 0.61mm, as drawn, 99.5%

GF31151887

Iron, tube, 200mm, outside diameter 2.0mm, inside diameter 1.6mm, wall thickness 0.2mm, as drawn, 99.5%

GF55566816

Iron, tube, 500mm, outside diameter 1.0mm, inside diameter 0.8mm, wall thickness 0.1mm, as drawn, 99.5%

GF83304828

Iron, tube, 1000mm, outside diameter 25.0mm, inside diameter 21mm, wall thickness 2mm, annealed, 99.5%

GF38919279

Iron, tube, 200mm, outside diameter 20.0mm, inside diameter 16mm, wall thickness 2.0mm, annealed, 99.5%

GF33572606

Iron, tube, 500mm, outside diameter 5.0mm, inside diameter 4.5mm, wall thickness 0.25mm, as drawn, 99.5%

GF30656077

Iron, tube, 200mm, outside diameter 10.0mm, inside diameter 7mm, wall thickness 1.5mm, annealed, 99.5%