Neurological effects of acute uranium exposure with and without stress.
Circulating uranium rapidly enters the brain and may cause adverse effects on the nervous system that are potentially modulated by stress. In this study, the neurological effects of a single intramuscular injection of 0, 0.1, 0.3, or 1 mg uranium/kg (as uranyl acetate, UA) in rats were examined in the presence and absence of stress. Treatment with UA produced time and dose-dependent increases in serum and regional brain uranium levels. While serum levels returned to control levels by day 30, brain levels remained elevated. Application of stress did not affect the distribution or retention of uranium. Exposure to 1 mg U/kg significantly decreased ambulatory activity, weight gain, forelimb grip strength and transiently impaired working memory. Effects on grip strength and memory were prevented by application of stress prior to uranium exposure. Striatal dopamine content was reduced by 30% 3 days after treatment with 1mg/kg (59+/-6 nmol/mg tissue versus 41+/-5 nmol/mg tissue), but levels returned to control 7 days after uranium exposure. The effect on dopamine was ameliorated by prior application of stress. Exposure to UA did not alter 3,4 dihydroxyphenylacetic acid (DOPAC) levels or numbers of D2 receptors in the striatum. No effect of uranium or stress was observed on levels of GABA, serotonin, norepinephrine, or glutathione (GSH) in the striatum, hippocampus, cerebellum, or cortex. These results indicate that single intramuscular exposures to uranium produce sustained elevation of brain uranium levels and at doses above 0.3 mg/kg can have adverse neurological effects. Application of stress prior to uranium administration modulates neurological effects, but the mechanism is not due to effects on uranium distribution. Uranium exposure also produced renal toxicity which must be considered to accurately assess the effects of uranium on neurological function.
Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA. barberd@mail.vetmed.ufl.edu
D S
DS
Barber
S K
SK
Hancock
A M
AM
McNally
J
J
Hinckley
E
E
Binder
K
K
Zimmerman
M F
MF
Ehrich
B S
BS
Jortner
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007273:Injections, Intramuscular; D007674:Kidney Diseases / Q000139:chemically induced; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014018:Tissue Distribution
D018377:Neurotransmitter Agents; D009942:Organometallic Compounds; C005460:uranyl acetate; D005978:Glutathione; D004298:Dopamine; D003345:Corticosterone