Lack of association between PSA‐NCAM expression and migration in the rostral migratory stream of a Huntington's disease transgenic mouse model

Abstract

Huntington's disease is a neurodegenerative autosomal disorder characterized by selective loss of striatal and cortical neurons. The mammalian brain subventricular zone contains a population of neural precursors involved in postnatal neurogenesis. These newly generated cells migrate from the subventricular zone along the rostral migratory stream and differentiate into mature olfactory bulb neurons throughout adulthood. The establishment of this pathway depends upon a variety of molecules, including polysialylated neural cell adhesion molecule (PSA-NCAM). We used a murine model of Huntington's disease, the R6/2 transgenic mouse, and in vivo bromodeoxyuridine administration to label cells undergoing proliferation and to follow their migration along the rostral migratory stream. Bromodeoxyuridine labeling did not show any significant increase in proliferation of progenitor cells in symptomatic R6/2 mice, but migration of neuroblasts along the rostral migratory stream was significantly diminished. The decrease in neuroblast migration was not due to an alteration in the expression of PSA-NCAM along the rostral migratory stream since immunohistochemical analysis showed no significant differences between R6/2 and wild type mice. In addition, we used Fluoro-Jade C to evaluate apoptosis and demonstrated that the number of apoptotic cells in the rostral migratory stream is similar in affected and wild type animals, suggesting that cell death is not responsible for the differences observed in neuroblast migration. We conclude that in R6/2 mice, progenitor cells have an impaired migration in their route to the olfactory bulb, with accumulation of cells in the caudal rostral migratory stream that does not result from changes in PSA-NCAM expression and/or cell death.