Marked differences in cholesterol synthesis between neurons and glial cells from postnatal rats

Abstract

Neurons have a high demand for cholesterol to develop and maintain membrane‐rich structures like axons, dendrites and synapses, but it remains unclear, whether they can satisfy their need by costly de novo synthesis. To address this, we compared cholesterol synthesis in serum‐free cultures of highly purified CNS neurons and glial cells from postnatal rats. We observed marked cell‐specific differences: Compared with glial cells, neurons showed different profiles of biosynthetic enzymes, post‐squalene precursors and cholesterol metabolites, and they produced cholesterol less efficiently, possibly because of very low levels of lanosterol‐converting enzymes. Astrocytes responded to inhibition of cholesterol synthesis with a much stronger up‐regulation of biosynthetic enzymes than neurons. Our results support the idea that neurons cannot produce cholesterol efficiently and that they depend on an external source of this lipid.

β-Amyloid Inhibits Protein Prenylation and Induces Cholesterol Sequestration by Impairing SREBP-2 Cleavage

“…The consequences of cholesterol synthesis inhibition in neurons are unclear. Neurons have lower rate of cholesterol synthesis than glia (Nieweg et al, 2009), and in adulthood, neurons might not synthesize cholesterol but outsource cholesterol from astrocytes (Fünfschilling et al, 2007;Aqul et al, 2011), although some studies showed that neurons might maintain some level of cholesterol synthesis (Valdez et al, 2010). Our data suggest that inhibition of cholesterol synthesis per se is not a direct cause of neuronal death because cholesterol synthesis inhibition by pravastatin did not cause neuronal death (de Chaves et al, 1997;Saavedra et al, 2007).…”

Disruption of astrocyte-neuron cholesterol cross talk affects neuronal function in Huntington’s disease

“…Of note, proteome-wide mapping of cholesterol-interacting proteins in mammalian cells reveals that most of these proteins are linked to neurological disorders. 54 Neurons produce cholesterol less efficiently than glial cells 55 and the appearance of most synapses in the developing brain is temporally and spatially coincident with astrocyte development, suggesting that synapse formation may depend on astrocytes-derived cholesterol. 56 Changes in cholesterol pathways and in apoE expression have been also associated to NMDA-mediated excitotoxicity.…”

Dysregulation of Plasmalogen Homeostasis Impairs Cholesterol Biosynthesis

“…Therefore, the regulation of plasmalogen synthesis most likely plays a pivotal role in the homeostasis of cholesterol especially in the central nervous system. Neurons do not efficiently synthesize cholesterol and mainly take up the cholesterol produced by astrocytes (74), hence suggesting that regulation of plasmalogen homeostasis unequivocally contributes to regulation of cholesterol synthesis in astrocytes. Our findings reported here open a way to address cholesterol homeostasis involving plasmalogen physiology.…”