BDNF modulates Apolipoprotein E mediated cholesterol trafficking between astrocytes and neurons.

Brain-derived neurotrophic factor (BDNF) exerts multiple biological functions in the central nervous system (CNS). It regulates neuronal survival, differentiation and plasticity by activating the receptor TrkB. BDNF levels have been found to be reduced in brain samples of Alzheimer's disease (AD) patients. Alterations in cholesterol homeostasis have also been suggested to play a role in AD. An open question is whether BDNF regulates lipid biosynthesis and metabolism. It was previously reported that BDNF elicits neuronal cholesterol biosynthesis for the development of presynaptic functions in the CNS, but its ability to modulate cholesterol trafficking between astrocytes and neurons was not yet clarified. Major aims of our work were to study BDNF effect on cholesterol efflux and Apolipoprotein E production from astrocytes, and cholesterol incorporation into neurons. The results shows that BDNF significantly increases the synthesis of Apolipoprotein E, which plays a key role in modulating lipid and beta amyloid homeostasis. Also BDNF stimulated cholesterol efflux from astrocytes, by enhancing the expression of ABC transporters. On the other hand, the uptake of cholesterol proteoliposomes in neuronal cells was downregulated by BDNF. These data highlight an additional role of BDNF in cholesterol homeostasis within CNS. A better understanding of the mechanisms by which neurotrophins regulate lipid metabolism is an intriguing issue that will provide a framework for future studies.