EndoN treatment allows neuroblasts to leave the rostral migratory stream and migrate towards a lesion within the prefrontal cortex of rats

Abstract

The binding properties of neural cell adhesion molecule are modulated by a polysialic acid moiety. This plays an important role in the migration of adult born neuroblasts from their area of origin, the subventricular zone, towards the olfactory bulb. Polysialisation increases the migration speed of the cells and helps to prevent the neuroblasts from leaving their migration route, the rostral migratory stream. Here, we evaluated the potential of intraventricular application of endoneuraminidase-N, an enzyme that specifically cleaves polysialic acid from neural cell adhesion molecule, in a rat model for structural prefrontal cortex damage. As expected, endoneuraminidase-N caused the rostral migratory stream to become wider, with a less uniform cellular orientation. Furthermore, endoneuraminidase-N treatment caused the neuroblasts to leave the rostral migratory stream and migrate towards the lesioned tissue. Despite the neuroblasts not being differentiated into neurons after a survival time of three weeks, this technique provides a solid animal model for future work on the migration and differentiation of relocated neuroblasts and might provide a basis for a future endogenous stem cell-based therapy for structural brain damage. The experiments were approved by the local animal care committee (522-27-11/02-00, 115; Senatorin für Wissenschaft, Gesundheit und Verbraucherschutz, Bremen, Germany) on February 10, 2016.

Keywords

• endogenous stem cells; endoneuraminidase; neural cell adhesion molecule; neuroblast migration; olfactory bulb; polisialic acid; structural brain damage; subventricular zone