Regulation of cholesterol biosynthetic pathway in different regions of the rat central nervous system

Abstract

In this study, we investigated the regulatory network of the key and rate-limiting enzyme of cholesterol biosynthetic pathway, the 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR) in different brain regions, to add new insight about lipid metabolism and physiology in the central nervous system (CNS). HMGR levels and activation state and the proteins involved in the enzyme regulatory network were analysed by Western blot in hippocampus, cortex, cerebellum and brain stem of adult male rats. HMGR protein level and phosphorylation state exhibit a specific pattern in each brain area analysed, according to the levels and activation state of the proteins responsible for the short- and long-term regulation of the enzyme. Moreover, low-density lipoprotein receptor expression displays a similar trend to that of HMGR. The obtained data indicate that cholesterol biosynthesis could be differently modulated in each brain region in adult male rat and emphasize marked differences in HMGR and low-density lipoprotein receptor regulation. The results provide new insights into the intricate network that regulates cholesterol homoeostasis in the adult CNS in connection with the regional needs of this molecule.