Rosuvastatin reduces gliosis and the accelerated weight gain observed in WT and ApoE-/- mice exposed to a high cholesterol diet.
The influence of a high cholesterol (HC) diet on brain pathology is being recognized increasingly and is of immense interest. Previous findings from our laboratory demonstrated that a high cholesterol diet increases gliosis, astrocytic reactivity and neuroinflammation in both wild type (WT) and apolipoprotein knockout (ApoE-/-) mice. In the present study, we analyzed whether this increase in astrocytic reactivity, monitored by the number of cells in the hippocampus labelled with glial fibrillary acidic protein (GFAP), could be reduced by the use of rosuvastatin, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase. Furthermore, we studied the effect of rosuvastatin on changes in lipoprotein levels and weight gain, and their correlation to gliosis, in mice fed a high cholesterol diet. A significant increase in weight, total-cholesterol (TC) and low-density lipoprotein (LDL) levels were observed in WT and ApoE-/- mice on a HC diet. The number of GFAP labelled cells was found to be significantly increased in mice on a HC diet and reduced in rosuvastatin-treated WT and ApoE-/- mice on a HC diet. A significant reduction of weight, total-cholesterol and LDL levels was observed in rosuvastatin-treated WTHC mice. Significant correlations were found between changes in body weight, GFAP labelled cells and plasma total-cholesterol levels in WT and ApoE-/- mice. However, the correlations were found to be weaker for the GFAP labelled cells in the ApoE-/- mice. The results indicate that the observed reduction of gliosis by rosuvastatin treatment may be due to mechanisms that are independent of its lipid-lowering effect.
Famer
Daniel
D
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.
Crisby
Milita
M
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D002452:Cell Count; D002784:Cholesterol / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D008078:Cholesterol, LDL / Q000378:metabolism; D005464:Fluorobenzenes / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced* / Q000517:prevention & control*; D006624:Hippocampus / Q000166:cytology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D005904:Glial Fibrillary Acidic Protein; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002784:Cholesterol