The novel synthetic microneurotrophin BNN27 protects mature oligodendrocytes against cuprizone-induced death, through the NGF receptor TrkA

Abstract

BNN27, a member of a chemical library of C17-spiroepoxy derivatives of the neurosteroid DHEA, has been shown to regulate neuronal survival through its selective interaction with NGF receptors (TrkA and p75^NTR), but its role on glial populations has not been studied. Here, we present evidence that BNN27 provides trophic action (rescue from apoptosis), in a TrkA-dependent manner, to mature oligodendrocytes when they are challenged with the cuprizone toxin in culture. BNN27 treatment also increases oligodendrocyte maturation and diminishes microglia activation in vitro. The effect of BNN27 in the cuprizone mouse model of demyelination in vivo has also been investigated. In this model, that does not directly involve the adaptive immune system, BNN27 can protect from demyelination without affecting the remyelinating process. BNN27 preserves mature oligodendrocyte during demyelination, while reducing microgliosis and astrogliosis. Our findings suggest that BNN27 may serve as a lead molecule to develop neurotrophin-like blood–brain barrier (BBB)-permeable protective agents of oligodendrocyte populations and myelin, with potential applications in the treatment of demyelinating disorders.

Main Points

• The novel steroid derivative BNN27 protects OLs from apoptosis when they are challenged in vitro with the cuprizone toxin, in a TrkA-dependent manner. In addition, BNN27 regulates OLs during demyelination in vivo and reduces microgliosis.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2qDfPTz
via IFTTT