Research article

Survival of adult neurons lacking cholesterol synthesis in vivo

Ursula Fünfschilling , Gesine Saher , Le Xiao , Wiebke Möbius and Klaus-Armin Nave

Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein Strasse 3, D-37075 Göttingen, Germany

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BMC Neuroscience 2007, 8:1doi:10.1186/1471-2202-8-1

Published:	2 January 2007

Abstract

Background

Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown.

Results

Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function.

Conclusion

We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.