Choline acetyltransferase activity and vesamicol binding in Rett syndrome and in rats with nucleus basalis lesions.
The decline in choline acetyltransferase activity has been identified previously within the brains of patients with Rett syndrome and Alzheimer's disease. The level of [3H]vesamicol binding to a terminal vesicular acetylcholine transporter is inversely related to the decline in cortical choline acetyltransferase activity in Alzheimer's disease, which may be due to compensatory processes within surviving cholinergic terminals. In order to investigate whether similar cholinergic compensatory processes are present in the Rett syndrome brain and are altered by normal aging, we investigated the density of cholinergic vesicular transporters in (i) the brains of Rett syndrome patients, and (ii) young and old rats with experimentally-induced cholinergic cell loss. In Rett syndrome, a significant decline in choline acetyltransferase activity within the putamen and thalamus was directly correlated with a decline in [3H]vesamicol binding. In both young and old rats, basal forebrain lesions decreased cortical choline acetyltransferase activity significantly, while [3H]vesamicol binding was unchanged. In contrast to young and old lesioned rats and patients with Alzheimer's disease, cholinergic cells in the brains of patients with Rett syndrome do not compensate for the loss of cholinergic cells by increasing acetylcholine vesicular storage.
Wenk
G L
GL
Arizona Research Laboratories, Division of Neural Systems, memory & Aging, University of Arizona, Tucson 85724, USA.
Mobley
S L
SL
D000109:Acetylcholine / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D009467:Neuromuscular Depolarizing Agents / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D011699:Putamen / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015518:Rett Syndrome / Q000201:enzymology / Q000378:metabolism*; D013788:Thalamus / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; C006189:vesamicol; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine