Abstract Title:

Inhibition of neuronal cholesterol biosynthesis with lovastatin leads to impaired synaptic vesicle release even in the presence of lipoproteins or geranylgeraniol.

Abstract Source:

J Neurochem. 2011 Sep 7. Epub 2011 Sep 7. PMID: 21899539

Abstract Author(s):

Tiffany Mailman, Manoj Hariharan, Barbara Karten

Article Affiliation:

Department of Biochemistry and Molecular Biology and Neuroscience Institute, Dalhousie University, Halifax, Nova Scotia, Canada.


Cholesterol is highly enriched in the brain, and plays a key role in synapse formation and function. The brain does not derive cholesterol from the circulation; instead, the majority of cholesterol is made in glia and secreted in form of lipoproteins. Neurons can synthesize cholesterol, but the extent of neuronal cholesterol biosynthesis in the adult brain is unknown. Cholesterol biosynthesis inhibitors of the statin family are widely used to lower circulating cholesterol and cardiovascular risk. Lipophilic statins can cross the blood brain barrier and inhibit brain cholesterol biosynthesis with possible consequences for synaptic cholesterol homeostasis. We have investigated the effects of lovastatin on synapse maturation and synaptic vesicle release. Treatment of primary hippocampal neurons with low levels of lovastatin for one week reduced synapse density and impaired synaptic vesicle release. Neither lipoproteins nor geranylgeraniol fully counteracted the lovastatin-induced decrease of synaptic vesicle exocytosis, even when cholesterol depletion was prevented. In contrast, restoration of neuronal cholesterol synthesis with mevalonate prevented defects in vesicle exocytosis without fully normalizing neuronal cholesterol content. These results raise the possibility that chronic exposure of neurons to lipophilic statins may affect synaptic transmission, and indicate that hippocampal neurons need a certain level of endogenous cholesterol biosynthesis.

Print Options

Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2022 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.