Food Restriction Counteracts Dexamethasone-Induced Downregulation of Genes Involved in Cholesterol Homeostasis in Rat Brain during Aging
2022
Authors:
Ćirić, JelenaTešić, Vesna
Milovanović, Nikola
Jovanović Macura, Irena
Ivković, Sanja
Kanazir, Selma
Perović, Milka
Document Type:
Article (Published version)
Metadata
Show full item recordAbstract:
Glucocorticoids are the most potent anti-inflammatory agents known. Limited in vivo data are available to characterize the mechanism underlying their cognitive side effects and transient occurrence of steroid psychosis. Cholesterol is important for proper neurotransmission and brain plasticity, and disruption of its homeostasis in the brain has been closely associated with memory decline during aging and in age-related neurodegenerative disorders. In the present study, we assessed the direct effects of dexamethasone, a potent synthetic glucocorticoid, on the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24S-hydroxylase (CYP46A1), major enzymes involved in cholesterol synthesis, metabolism, and excretion, respectively. The effects of the dexamethasone were examined during aging, in the cortex and hippocampus of 6-, 12- and 18-month-old rats, and following long-term food restriction (FR). The most prominent change observed was the age-related decrease in ApoE mRNA regardless of the food regimen applied. In animals kept on FR, this decrease was accompanied by an increase in the mRNA expression of HMGCR and CYP46A1. The present study also demonstrates that food restriction reversed most of the dexamethasone-induced changes in the expression of genes involved in regulation of cholesterol homeostasis in aging rats, in a region-specific manner.
Keywords:
cortex; every-other-day feeding; hippocampus; intermittent fasting; lipid metabolism; serum glucoseSource:
Brain Sciences, 2022, 12, 10, 1297-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/brainsci12101297
ISSN: 2076-3425
PubMed: 36291231
WoS: 000872599300001
Scopus: 2-s2.0-85140597090
URI
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9599456http://radar.ibiss.bg.ac.rs/handle/123456789/5172