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 in aged animals irradiated with (56)Fe particles involved alterations in muscarinic receptor sensitivity. In the present experiments, we determined whether increasing either membrane fluidity by exposure of striatal slices from irradiated ((56)Fe particles) animals to S-adenosyl-l-methionine (SAM) or GTP hydrolysis with Mg(2+) would reverse this (56)Fe-particle-induced loss of muscarinic receptor sensitivity, as has been observed in aged animals. Results indicated that, while increasing Mg(2+) concentrations in the incubation medium was effective in reducing the radiation effects, SAM was able to effect some reversal of the radiation effects only at the lower concentration (200 microM). These results suggest that similar mechanisms may be involved in the deficits in signal transduction seen after (56)Fe-particle irradiation to those seen in aging, and that these may include changes in the membrane structure or composition that could alter subsequent responsiveness of transduction pathways. The results further suggest that, as has been reported previously, (56)Fe-particle irradiation may accelerate brain aging, and that since these HZE particles contribute at least 1% of the dose that astronauts would receive from cosmic rays, long-term exposure on extended space flights (e.g. to Mars) may produce similar deficits that could have immediate or delayed effects on behavior.
Joseph
J A
JA
USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA.
Shukitt-Hale
B
B
McEwen
J
J
Rabin
B
B
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D004298:Dopamine / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D010095:Oxotremorine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D017356:Synchrotrons
D010095:Oxotremorine; D012436:S-Adenosylmethionine; D006160:Guanosine Triphosphate; D007501:Iron; D008274:Magnesium; D011188:Potassium; D004298:Dopamine