Aluminum alters cyclic AMP and cyclic GMP levels but not presynaptic cholinergic markers in rat brain in vivo.
Oral administration of 0.3% aluminum (citrate or sulfate salt) for 4 weeks significantly elevated adenosine 3',5'-monophosphate (cyclic AMP) levels in rat cortex, hippocampus, striatum and cerebellum. The largest effect observed was a 60% increase in cortical cyclic AMP levels in rats administered aluminum sulfate. The effects of orally administered aluminum on guanosine 3',5'-monophosphate (cyclic GMP) levels were less widespread. Dietary aluminum citrate only elevated cyclic GMP levels in the hippocampus, while aluminum sulfate caused significant increases in the cerebellum, hippocampus and striatum. Aluminum citrate administered i.c.v. (1 mumol, 2 weeks postadministration) elevated cyclic AMP levels in the cortex, but had no effect on cyclic GMP levels. Aluminum administered either orally or i.c.v. had no effect on in vivo acetylcholine levels. However, dietary aluminum citrate significantly reduced choline levels in the cortex, hippocampus and striatum. Aluminum administered i.c.v. had no effect on choline acetyltransferase activity or on high-affinity choline transport. These results indicate that: the metabolism of cyclic AMP and of cyclic GMP are more sensitive to aluminum than are presynaptic cholinergic processes; the metabolism of cyclic AMP is more sensitive to the effects of aluminum than is the metabolism of cyclic GMP; and cortical cAMP metabolism is the most sensitive to the presence of aluminum. Possible consequences of elevated levels of cyclic nucleotides induced by aluminum in the brain are proposed.
D000284:Administration, Oral; D000534:Alum Compounds; D000535:Aluminum / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology; D019343:Citric Acid; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000008:administration & dosage / Q000494:pharmacology
D000534:Alum Compounds; D002951:Citrates; D013431:Sulfates; D019343:Citric Acid; C041524:aluminum sulfate; D000535:Aluminum; D000242:Cyclic AMP; D002795:Choline O-Acetyltransferase; D006152:Cyclic GMP; D002794:Choline