title: Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.
abstract: BACKGROUND
  The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention.
  
  
  METHODS
  One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aβ), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated.
  
  
  RESULTS
  Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P < 0.05) and the expression of IL-1, TNF-α and GFAP in the brains had increased (P < 0.05). In the second week, the expression of FFA and APP in the brains, and the amount of apoptotic neurons, had increased (P < 0.05). In the third week, the levels of VEGF, Ox-LDL and Aβ had increased, and the expression of Claudin-5 had decreased in the brains (P < 0.05). In the fourth week, the levels of TC, LDL-C and the amount of apoptotic neurons had increased (P < 0.05). The correlation analysis showed a positive correlation among FFA, TNF-α, VEGF, ox-LDL, Aβ, GFAP and neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P < 0.05).
  
  
  CONCLUSIONS
  Hyperlipidemia may activate astrocytes by means of high levels of TG that will have direct toxic effects on the cerebral vessels and neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aβ, induce the secretion of VEGF, reduce the expression of tight junction protein Claudin-5 and change the permeability of blood-brain barriers to factors that could damage cerebral vessels and neurons.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, 410078, China.
authors.forename: Weichun
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, 410078, China.
authors.forename: He
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, 410078, China.
authors.forename: Jianfen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, 410078, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, 410078, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Central South University, Changsha, 410078, China. huminyu@csu.edu.cn.
authors.forename: Minyu
authors.initials: M
authors.lastname: Hu
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D062507:Claudin-5 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006949:Hyperlipidemias / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D008078:Cholesterol, LDL; D062507:Claudin-5; D005230:Fatty Acids, Nonesterified; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C099252:oxidized low density lipoprotein; C467498:vascular endothelial growth factor A, rat; D002097:C-Reactive Protein
keywords: Cerebral lipid; Cerebral vessels; Duration time; Hyperlipidemia; Neurons