Central nervous dysfunction in uremia.
The mechanisms of central nervous system dysfunction in uremia are multifactorial and only partially characterized. Studies using sealed presynaptic nerve terminals (synaptosomes) for in vitro ion transport and metabolism of neurotransmitter in chronic renal failure (CRF) neuronal cell culture and in vivo brain structure microdialysis generated significant new information. An increase in total calcium content of the cerebral cortex accompanied by increased levels of cytosolic calcium ([Ca(2+)]i) in synaptosomes are common findings in rats with CRF. Mechanisms leading to the increase in [Ca(2+)]i include increased calcium uptake mediated by parathyroid hormone and decreased activity of Na(+),K(+)-adenosine triphosphatase (ATPase) and Ca(2+)-ATPase of synaptosomes in CRF rats. Moreover, these synaptosomes respond inappropriately to depolarization, which can impair neurotransmitter metabolism. Brain gamma-aminobutyric acid content, norepinephrine, and acetylcholine release uptake and degradation are affected by uremia. These may lead to certain somatic, behavioral, and motor dysfunctions in uremia. Many derangements of the central nervous system in uremia appear to be mediated by secondary hyperparathyroidism of CRF because parathyroidectomy of animals with CRF prevented the increase in basal levels of [Ca(2+)]i and derangements in neurotransmitter metabolism. The role of other neurotoxins, such as guanidinosuccinic acid, are also reviewed.
Smogorzewski
M J
MJ
Division of Nephrology and Department of Medicine, the Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. smogorze@hsc.usc.edu
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001284:Atrophy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014511:Uremia / Q000150:complications*; D014700:Verapamil / Q000494:pharmacology
D018377:Neurotransmitter Agents; D010281:Parathyroid Hormone; D010743:Phospholipids; D000255:Adenosine Triphosphate; D014700:Verapamil; D002118:Calcium