Expression of cholesterol homeostasis genes in the brain  of the male rat is affected by age and dietary restriction.
Expression profiles of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), apolipoprotein E (ApoE) and cholesterol 24S-hydroxylase (CYP46), proteins involved in cholesterol biosynthesis, transport and excretion from the CNS, were analyzed in the rat cortex, hippocampus and cerebellum as a function of aging (6–24 months) and in response to long-term dietary restriction (DR). Age-related increases for all three mRNAs were observed, with the highest induction found for Cyp46 in the cortex and hippocampus of 24-month-old animals. DR maintained stable levels of Cyp46, HMGR, and ApoE mRNAs during aging, exhibiting an attenuating effect on age-related changes through specific temporal and regional pattern. Neither age nor DR had any prominent effects at the protein level, except for Cyp46 and ApoE protein levels in the hippocampus and cerebellum, respectively. Overall, the changes in the cerebellum were different from those in the cortex and hippocampus. Our results demonstrated a modulatory effect of DR on agerelated changes of CYP46, HMGR, and ApoE and suggest that the anti-aging effect of DR is in part mediated though transcriptional modulation of cholesterol metabolism genes in the rat brain.
Perovic
Milka
M
Laboratory of Molecular Neurobiology, Department of Neurobiology, Institute for Biological Research Sinisa Stankovic, University of Belgrade, Bul. D. Stefana 142, 11060 Belgrade, Serbia.
Mladenovic Djordjevic
Aleksandra
A
Smiljanic
Kosara
K
Tanic
Nikola
N
Rakic
Ljubisav
L
Ruzdijic
Sabera
S
Kanazir
Selma
S
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D031204:Caloric Restriction; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D000072556:Cholesterol 24-Hydroxylase; D006624:Hippocampus / Q000378:metabolism; D006706:Homeostasis; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation
D001057:Apolipoproteins E; D012333:RNA, Messenger; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase