Alpha-sialyl cholesterol reverses AF64A-induced deficit in passive avoidance response and depletion of hippocampal acetylcholine in mice.
1. The effect of alpha-sialyl cholesterol (alpha-SC; alpha-D-N-acetylneuraminyl cholesterol) on disturbances of the central cholinergic system induced by ethylcholine mustard aziridinium ion (AF64A) and by scopolamine were studied by means of a step-down passive avoidance response and locomotor activities in mice. The levels of acetylcholine (ACh) in certain regions of the brain were measured to assess the neurochemical recovery promoted by alpha-SC. 2. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) impaired the 24 h retention latencies of animals in a dose-dependent manner, and scopolamine (0.5 mg kg-1, i.p.) also impaired the retention performance. Administration of alpha-SC (1 and 4 mg kg-1, p.o.) once daily for 13 days improved the retention performance in AF64A-treated animals in a dose-dependent manner, but not in the scopolamine-treated animals. 3. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) and scopolamine (0.5 mg kg-1, i.p.) increased vertical and horizontal locomotor activities. alpha-SC dose-dependently attenuated the increase in locomotor activities induced by 2.5 nmol of AF64A, but not the locomotor activities caused by 5 or 10 nmol of AF64A, or scopolamine (0.5 mg kg-1, i.p.). 4. The deficit retention performance of AF64A-treated animals was associated with depletion of ACh levels in the hippocampus, but not in the septum or cerebral cortex. Administration of alpha-SC to AF64A-treated animals dose-dependently reversed the depletion of ACh levels in the hippocampus. 5. The results indicate that alpha-SC had significant effects after oral administration of AF64A-treated animals. The behavioural recovery promoted by alpha-SC may be based on the reversal of ACh depletion in the hippocampus.
Abe
E
E
Department of Pharmacology, School of Dentistry, Iwate Medical University, Morioka, Japan.
Murai
S
S
Masuda
Y
Y
Saito
H
H
Itoh
T
T
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001388:Aziridines / Q000037:antagonists & inhibitors*; D002788:Cholesterol Esters / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D012601:Scopolamine / Q000037:antagonists & inhibitors; D012794:Sialic Acids / Q000494:pharmacology*; D014118:Toxins, Biological
D001388:Aziridines; D002788:Cholesterol Esters; D012794:Sialic Acids; D014118:Toxins, Biological; C055195:N-acetylneuraminyl cholesterol; C044894:ethylcholine aziridinium; D012601:Scopolamine; D002794:Choline; D000109:Acetylcholine