Transthyretin knockout mouse nerves have increased lipoprotein lipase and sphingolipid content following crush.

Abstract

Transthyretin (TTR) knockout (KO) mice display increased levels of lipoprotein lipase (LPL) and impaired nerve regeneration. Given LPL potential role in the reutilization of myelin lipids following injury, we compared myelin lipid content in wild-type and TTR KO mice after nerve crush. We found that LPL is expressed not only in Schwann cells but also in dorsal root ganglia neurons and that its activity is increased in TTR KO mice following nerve injury. As a possible consequence of LPL increase in the regenerating nerve of TTR KOs, the sphingolipids sphingomyelin and galactocerebroside were augmented in the distal nerve stump. Given their ability to increase neurite outgrowth, upregulation of LPLand sphingolipids in a system with decreased capacity for nerve regeneration probably constitutes a compensatory mechanism.