Dietary beta-alanine results in taurine depletion and cerebellar damage in adult cats.
We have used the taurine analogue, beta-alanine, to perturb the taurine concentrations in taurine-supplemented and taurine-deprived adult cats. By using 5% beta-alanine in the drinking water for 20 weeks, both groups of cats had greatly reduced brain taurine concentrations. Taurine-supplemented cat brain accumulated relatively small amounts of beta-alanine whereas taurine-deprived cats accumulated large amounts of beta-alanine. The cerebellum of cats treated with beta-alanine had a number of pathological changes compared with similar cats drinking water alone. The changes were more severe in the taurine-deprived cats, and included reduced numbers of granule and Purkinje cells, with many of those remaining appearing pyknotic and dying. Long swollen fibers were seen in the white matter, resembling Rosenthal fibers described in some human cerebellar diseases. There was also prominent gliosis. Using antibodies to beta-alanine and taurine, beta-alanine was localized in Purkinje cell soma and dendrites, in Golgi II cells, and in some granule cells, especially in taurine-deprived cats treated with beta-alanine. Taurine appears to have been virtually eliminated from Purkinje and granule cells, and concentrated in Golgi II cells and glia. We conclude that beta-alanine is responsible for these neurotoxic pathological changes.
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Department of Developmental Biochemistry, New York State Office of Mental Retardation and Developmental Disabilities, Staten Island, USA.
Xu
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Sturman
J A
JA
D000284:Administration, Oral; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002415:Cats / Q000378:metabolism*; D002526:Cerebellar Diseases / Q000139:chemically induced* / Q000473:pathology; D002531:Cerebellum / Q000473:pathology*; D004032:Diet; D005260:Female; D005911:Gliosis / Q000139:chemically induced; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009751:Nutritional Requirements; D011689:Purkinje Cells / Q000473:pathology; D013654:Taurine / Q000008:administration & dosage / Q000172:deficiency*; D015091:beta-Alanine / Q000008:administration & dosage / Q000633:toxicity*
D009498:Neurotoxins; D015091:beta-Alanine; D013654:Taurine