Survival of adult neurons lacking cholesterol synthesis in vivo.
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.


CONCLUSIONS
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.
Fünfschilling
Ursula
U
Department of Neurogenetics, Max-Planck-Institute of Experimental Medicine, Hermann-Rein Strasse 3, D-37075 Göttingen, Germany. fuenfschilling@em.mpg.de
Saher
Gesine
G
Xiao
Le
L
Möbius
Wiebke
W
Nave
Klaus-Armin
KA
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000502:physiology*
D002784:Cholesterol; D013186:Farnesyl-Diphosphate Farnesyltransferase