APOLIPOPROTEIN-E EXPRESSION IN THE CEREBELLUM OF NORMAL AND HYPERCHOLESTEROLEMIC RABBITS

We have studied the expression of apolipoprotein E (ApoE) mRNA in the cerebella of control and experimental rabbits fed with a cholesterol-r ich diet for 8 weeks. Cholesterol-treated rabbits show a dramatic incr ease in serum cholesterol levels; however, no significant variations i n the expression level of cerebellar ApoE mRNA were found in compariso n to control rabbits. In addition, no differences were observed betwee n control and hypercholesterolemic rabbits in the in situ hybridizatio n pattern of ApoE mRNA on cerebellar cortex sections. ApoE mRNA was lo calized in astroglial processes assocciated with Purkinje cell bodies and dendrites, granule cell clusters, blood vessels and nerve fibers o f the white matter. No expression of ApoE mRNA was observed in Purkinj e and granule cell neurons. Polarized light examination of cryostat ce rebellar sections revealed the absence of cholesterol-rich microglia/m acrophage cells induced by the hypercholesterolemia. In this way, neit her reactive microglial cells nor perivascular phagocytes were found b y ultrastructural analysis in hypercholesterolemic conditions. The pat tern of glial fibrillary acidic protein of the astroglial cells of the cerebellar cortex as well as their nuclear size were unchanged follow ing cholesterol treatment, indicating the absence of astroglial activa tion induced by hypercholesterolemia. Our results suggest that cerebel lar ApoE does not contribute to the general cholesterol homeostasis ou tside of the brain and supports the view that this cerebellar ApoE is involved in paracrine and autocrine functions particularly related wit h synpase turnover and membrane remodelling of astroglial cells.