PERIPHERAL SENSORY NERVE DEFECTS IN APOLIPOPROTEIN-E KNOCKOUT MICE

Apolipoprotein E (apoE), a plasma lipoprotein involved in lipid metabo lism, is also proposed to have important functions within the central and peripheral nervous systems. To investigate the function of apoE in the peripheral nervous system, we examined the structure of sciatic n erves in apoE-deficient (apoE KO) mice. In the normal peripheral nervo us system, apoE is produced by nonmyelinating Schwann cells, suggestin g a role for apoE in the support of unmyelinated thermal and nocicepti ve sensory afferents. Using electron microscopy, we have found that ap oE KO mice have abnormal and reduced numbers of unmyelinated axons wit hin the sciatic nerve. ApoE KO unmyelinated axons are irregularly shap ed and separated by very little Schwann cell cytoplasm. ApoE KO myelin ated fibers and myelin are ultrastructurally normal. Consistent with t hese morphological findings, apoE KO mice display reduced sensitivity to noxious thermal stimuli. These data provide in vivo support for the hypothesis that apoE promotes neuronal health and survival. (C) 1998 Academic Press.