The influence of simvastatin, atorvastatin and high-cholesterol diet on acetylcholinesterase activity, amyloid beta and cholesterol synthesis in rat brain

Cholesterol is a critical component of eukaryotic membranes, where it contributes to regulating transmembrane signaling, cell–cell interaction, and ion transport. Dysregulation of cholesterol levels in the brain may induce neurodegenerative diseases, such as Alzheimer’s disease, Parkinson disease, and Huntington disease. We previously reported that augmenting membrane cholesterol level regulates ion channels by decreasing the level of phosphatidylinositol 4,5-bisphosphate (PIP2), which is closely related to β-amyloid (Aβ) production. In addition, cholesterol enrichment decreased PIP2 levels by increasing the expression of the β1 isoform of phospholipase C (PLC) in cultured cells. In this study, we examined the effect of a high-cholesterol diet on phospholipase C (PLCβ1) expression and PIP2 levels in rat brain. PIP2 levels were decreased in the cerebral cortex in rats on a high-cholesterol diet. Levels of PLCβ1 expression correlated with PIP2 levels. However, cholesterol and PIP2 levels were not correlated, suggesting that PIP2 level is regulated by cholesterol via PLCβ1 expression in the brain. Thus, there exists cross talk between cholesterol and PIP2 that could contribute to the pathogenesis of neurodegenerative diseases.

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Effect of lactation on cholesterol synthesis in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1985.249.2.g203 ◽

1985 ◽

Vol 249 (2) ◽

pp. G203-G208 ◽

Cited By ~ 1

Author(s):

K. R. Feingold ◽

A. H. Moser

Keyword(s):

Cholesterol Synthesis ◽

Feedback Inhibition ◽

Tritiated Water ◽

High Cholesterol Diet ◽

Cholesterol Diet ◽

Hepatic Cholesterol ◽

High Cholesterol ◽

Functional Changes ◽

Hepatic Cholesterol Synthesis ◽

The Difference

Lactation induces a variety of morphological and functional changes in the gastrointestinal tract. In the present study we employed tritiated water as the substrate to demonstrate that in the intact rat lactation results in a twofold increase in cholesterol synthesis in the small intestine. Feeding a high-cholesterol diet did not markedly inhibit small intestinal cholesterol synthesis in either control or lactating animals, and the difference in cholesterol synthesis between the two groups persisted. In the large intestine, cholesterol synthesis is increased threefold in the lactating animals, and feeding a high-cholesterol diet did not affect synthesis in either the control or lactating animals. In the liver, lactation stimulated cholesterol synthesis, and quantitatively this increase in hepatic cholesterol synthesis is much greater than the increase observed in the intestines. Feeding the rats a high-cholesterol diet markedly inhibited hepatic cholesterol synthesis in both control and lactating animals, a finding that demonstrates that the feedback inhibition of cholesterol synthesis in the liver is not impaired by lactation. In the lactating animals, the quantity of labeled cholesterol in 1 ml of serum is 2.4 times greater than observed in controls. Feeding the rats a high-cholesterol diet markedly decreased the quantity of labeled cholesterol in the serum in both groups and obliterated the difference between control and lactating animals. This suggests that the increased hepatic cholesterol synthesis in the lactating animals is responsible for the differences in labeled cholesterol in the serum. Cholesterol feeding also reduced the quantity of labeled cholesterol localized to the mammary glands in lactating animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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