Magnesium activation of GTP hydrolysis or incubation in S-adenosyl-L-methionine reverses iron-56-particle-induced decrements in oxotremorine enhancement of K+-evoked striatal release of dopamine

Previous research has determined that the deficits in motor behavior seen i n aged animals irradiated with Fe-56 particles involved alterations in musc arinic receptor sensitivity. In the present experiments, we determined whet her increasing either membrane fluidity by exposure of striatal slices from irradiated (56Fe particles) animals to S-adenosyl-L-methionine (SAM) or GT P hydrolysis with Mg2+ would reverse this Fe-56-particle-induced loss of mu scarinic receptor sensitivity, as has been observed in aged animals. Result s indicated that, while increasing Mg2+ concentrations in the incubation me dium was effective in reducing the radiation effects, SAM was able to effec t some reversal of the radiation effects only at the lower concentration (2 00 mu M). These results suggest that similar mechanisms may be involved in the deficits in signal transduction seen after Fe-56-particle irradiation t o those seen in aging, and that these may include changes in the membrane s tructure or composition that could alter subsequent responsiveness of trans duction pathways. The results further suggest that, as has been reported pr eviously, Fe-56-particle irradiation may accelerate brain aging, and that s ince these HZE particles contribute at least 1% of the dose that astronauts would receive from cosmic rays, long-term exposure on extended space fligh ts (e.g. to Mars) may produce similar deficits that could have immediate or delayed effects on behavior. (C) 1999 bg Radiation Research Society.