Chronic ingestion of uranyl nitrate perturbs acetylcholinesterase activity and monoamine metabolism in male rat brain.
Recent animal studies have shown that uranium can reach the brain after chronic exposure. However, little information is available on the neurological effects of chronic long-term exposure to uranium. In the present study, the effects during 1.5, 6 and 9-month periods of chronic ingestion of uranyl nitrate (UN) in drinking water (40 mg of uranium per litre) on cholinergic acetylcholinesterase (AChE) activity and on dopaminergic and serotoninergic metabolisms were investigated in several areas of male Srague Dawley rat brains. Uranium brain accumulation and distribution was also investigated after 1.5 and 9 months. Both after 1.5, 6 and 9 months of exposure, AChE activity was unaffected in the striatum, hippocampus and frontal cortex. Nevertheless, AChE activity was transitionally perturbed in the cerebellum after 6 months of exposure. After 1.5 months of exposure, DA level increased in hypothalamus. After 6 months of exposure, a tiny but significant modification of the DAergic turnover ratio was detected in the frontal cortex. And after 9 months, UN produced a significant decrease in the 5HIAA level and the 5HTergic turn-over ratio in the frontal cortex and also a decrease in the DOPAC level and DAergic turn-over ratio in the striatum. Uranium brain accumulation was statistically significant in striatum after 1.5 months and in striatum, hippocampus and frontal cortex after 9 months of exposure. Although neurochemical changes did not always correlated with increased accumulation of uranium in specific areas, these results suggest that chronic ingestion of UN can cause chronic and progressive perturbations of physiological level of neurotransmitter systems. Considering previous reports on behavioural uranium-induced effects and the involvement of neurotransmitters in various behavioural processes, it would be crucial to determine whether these neurochemical disorders were accompanied by neurobehavioral deficits even at 40 mg of uranium per litre exposure.
Bussy
C
C
Institut de Radioprotection et de Sûreté Nucléaire, Direction de la radioprotection de l'homme, Service de radiobiologie et d'épidémiologie, Laboratoire de radiotoxicologie expérimentale, BP166, 26702 Pierrelatte Cedex, France.
Lestaevel
P
P
Dhieux
B
B
Amourette
C
C
Paquet
F
F
Gourmelon
P
P
Houpert
P
P
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002800:Cholinesterase Inhibitors; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000502:physiology; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology; D014501:Uranium / Q000378:metabolism; D014502:Uranyl Nitrate / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
D015306:Biogenic Monoamines; D002800:Cholinesterase Inhibitors; D014502:Uranyl Nitrate; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D014501:Uranium; D006897:Hydroxyindoleacetic Acid; D000110:Acetylcholinesterase; D004298:Dopamine