Conclusion
Vomeronasal receptor neurons are less susceptible against NPC1 pathology than olfactory receptor neurons. Compared to control mice, however, the VNE of Npc1-/- mice displays an increased neuroregenerative potential, indicating compensatory cell renewal.
Methods
Proliferation in the VNE and OE was assessed by applying a bromodeoxyuridine (BrdU) protocol. We further compared the immunoreactivities of anti-olfactory marker protein (OMP), and the lysosomal marker cathepsin-D in both epithelia. To investigate if degenerative effects of both olfactory systems can be prevented or reversed, some animals were treated with a combination of miglustat/allopregnanolone/2-hydroxypropyl-cyclodextrin (HPβCD), or a monotherapy with HPβCD alone.
Results
Using BrdU to label dividing cells of the VNE, we detected a proliferation increase of 215% ± 12% in Npc1-/- mice, and 270% ± 10% in combination- treated Npc1-/- animals. The monotherapy with HPβCD led to an increase of 261% ± 10.5% compared to sham-treated Npc1-/- mice. Similar to the OE, we assessed the high regenerative potential of vomeronasal progenitor cells. OMP reactivity in the VNE of Npc1-/- mice was not affected, in contrast to that observed in the OE. Concomitantly, cathepsin-D reactivity in the VNE was virtually absent.