Neurotransmitter metabolites, enzymes and receptors in experimental scrapie.
A comprehensive study has been made of metabolites, enzymes and receptors for a variety of neurotransmitter systems in different parts of the CNS from mice affected with 139A scrapie. Studies were made at the early clinical stage so as to minimise secondary alterations in terminally sick mice. Even though histological lesions (vacuolation) are widespread in the CNS in this model of scrapie, no consistent neurochemical changes were found in mid- or anterior brain. In the cerebellum, the activity of glutamic acid decarboxylase was reduced and the binding of [3H]muscimol to gamma-aminobutyric acid receptors was increased. In the brain stem, the concentration of 5-hydroxyindoleacetic acid (5-HIAA) was increased and there was a reduced binding of appropriate ligands to serotonin and to muscarinic cholinergic receptors. In the spinal cord, the activity of choline acetyl transferase was reduced and the concentration of 5-HIAA was increased. The extent of these alterations was about 20-40% of control values. The specificity of these changes for a few neurotransmitter systems in hind brain and spinal cord raised the possibility of their being a primary cause of clinical disease and led us to study a different scrapie model. Present and published findings show that an increased concentration of 5-HIAA, some alterations in the binding properties of serotonin receptors and a decreased number of muscarinic receptor sites are common to both 139A scrapie in CW mice and 263K scrapie in hamsters.
Cross
A J
AJ
Kimberlin
R H
RH
Crow
T J
TJ
Johnson
J A
JA
Walker
C A
CA
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006224:Cricetinae; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000032:analysis; D012608:Scrapie / Q000378:metabolism*
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D006897:Hydroxyindoleacetic Acid; D004299:Dopamine beta-Hydroxylase; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase