Lipid alterations in excitotoxic brain injury

Abstract

Lipids are especially important in the central nervous system (CNS). Changes in brain lipid levels due to their increased or decreased synthesis or metabolism may result in homeostatic dysregulation and ultimately neurodegeneration. This study used kainate-induced in vivo and in vitro excitotoxic neurodegenerative models, suggesting that dysregulation of two important membrane lipids, cholesterol and ceramide. Increased cholesterol, cholesterol oxidative products (24-hydroxycholesteol and 7-ketocholesterol), and ceramide levels were found after kainate injury in vitro and in vivo. This was accompanied by the increased expression of cholesterol 24-hydroxylase and serine palmitoyltransferase. Altered cholesterol and ceramide metabolisms after kainate injury may lead to or accelerate neurodegeneration and therefore be important in the pathogenesis of neurodegenerative diseases. Intervention of dysregulated lipid metabolism may confer neuroprotection. The results of present study also indicate the neuroprotective effect of a lipid binding protein, apolipoprotein D (apoD).