The influence of simvastatin, atorvastatin and high-cholesterol diet on acetylcholinesterase activity, amyloid beta and cholesterol synthesis in rat brain.
OBJECTIVE
There is evidence to suppose that cholesterol-lowering medicine might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present study was to investigate the potential influence of statins and cholesterol diet on selected parameters relevant to Alzheimer's disease pathophysiology.


METHODS
For 15 days, rats were orally administered simvastatin (10 or 20mg/kg b.wt.), atorvastatin (10 or 20mg/kg b.wt.), or aqua (control group); and one group was fed high-cholesterol (2%) diet. At the end of experiments brain (and plasma) cholesterol, lathosterol, hydroxymethylglutaryl-coenzyme A reductase protein, acetylcholinesterase activity, amyloid beta (40 and 42) and cholesterol synthesis rate (using the incorporation of deuterium from deuterated water) were determined and statistically compared to those of aqua.


RESULTS
Both statins were able to lower cholesterol in the plasma, but none elicited an effect on total brain cholesterol. Significant reductions of brain lathosterol and cholesterol synthesis rate were observed after simvastatin and atorvastatin treatment. Acetylcholinesterase activity, amyloid beta and hydroxymethylglutaryl-coenzyme A reductase levels remained unaffected by the two drugs.


CONCLUSIONS
This study brings additional evidence of a role for statins in cholesterol synthesis in the brain. Our data question the relationship between amyloid beta, acetylcholinesterase activity and cholesterol synthesis in the rat brain as well as the assumption about no exchange between peripheral and brain cholesterol pools.
Cibickova
Lubica
L
2nd Department of Medicine, Charles University in Prague, Medical Faculty in Hradec Kralove and University Hospital Hradec Kralove, Czech Republic. cibickova@seznam.cz
Hyspler
Radomir
R
Radomir
Hyspler
H
Micuda
Stanislav
S
Stanislav
Micuda
M
Cibicek
Norbert
N
Norbert
Cibicek
C
Zivna
Helena
H
Helena
Zivna
Z
Jun
Daniel
D
Daniel
Jun
J
Ticha
Alena
A
Alena
Ticha
T
Brcakova
Eva
E
Eva
Brcakova
B
Palicka
Vladimir
V
Vladimir
Palicka
P
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002784:Cholesterol / Q000096:biosynthesis*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004032:Diet; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008297:Male; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D000110:Acetylcholinesterase