Decreased demand for olfactory periglomerular cells impacts on neural precursor cell viability in the rostral migratory stream

Abstract

The subventricular zone (SVZ) provides a constant supply of new neurons to the olfactory bulb (OB). Different studies have investigated the role of olfactory sensory input to neural precursor cell (NPC) turnover in the SVZ but it was not addressed if a reduced demand specifically for periglomerular neurons impacts on NPC-traits in the rostral migratory stream (RMS). We here report that membrane type-1 matrix metalloproteinase (MT1-MMP) deficient mice have reduced complexity of the nasal turbinates, decreased sensory innervation of the OB, reduced numbers of olfactory glomeruli and reduced OB-size without alterations in SVZ neurogenesis. Large parts of the RMS were fully preserved in MT1-MMP-deficient mice, but we detected an increase in cell death-levels and a decrease in SVZ-derived neuroblasts in the distal RMS, as compared to controls. BrdU-tracking experiments showed that homing of NPCs specifically to the glomerular layer was reduced in MT1-MMP-deficient mice in contrast to controls while numbers of tracked cells remained equal in other OB-layers throughout all experimental groups. Altogether, our data show the demand for olfactory interneurons in the glomerular layer modulates cell turnover in the RMS, but has no impact on subventricular neurogenesis.

Neuronal precursor cells with dopaminergic commitment in the rostral migratory stream of the mouse

“…Indeed, an increased rate of apoptosis occurred, supporting the hypothesis of an intrinsic regulation of dopaminergic cell turnover in the OB maintaining the number of dopaminergic cells at a constant level. Consistently, prior work suggested the existence of an intrinsic signal pathway adapting cell proliferation in the RMS to the demand of periglomerular interneurons in the OB 9,28,29 .…”

“…It harbors adult NSCs and has an important role in regulating of PGL cell number and the dopaminergic cell fate. As suggested in prior work 29 , the RMS is indeed able to adapt to and compensate specific conditions, such as reduced migration of SVZ-derived neuroblasts, by enhancing its proliferative activity.…”

Adult Born Periglomerular Cells of Odorant Receptor Specific Glomeruli

“…The maturational stage of BrdU positive cells was assessed by double labeling experiments with an antibody for doublecortin, which is considered a marker for neuroblasts (Brown et al, 2003 ). The finding that no cells were co-stained for BrdU and DCX at the time point of analyses suggests that BrdU labeled cells were beyond a stage detectable by DCX labeling and thus cannot be considered as neuroblasts; this observation is in line with the findings of previous studies (Belluzzi et al, 2003 ; Whitman and Greer, 2007 ; García-González et al, 2016 ; Langenfurth et al, 2016 ). The notion that a low number of BrdU positive cells in the vicinity of OR37 glomeruli might reflect a generally low number of neuroblasts reach the OR37-area in the antero-ventral region of the bulb was supported by the finding that also less DCX stained cells were found for OR37A glomeruli compared to OR18-2 and OR256-17 glomeruli.…”

Olfactory memory is enhanced in mice exposed to extremely low-frequency electromagnetic fields via Wnt/β-catenin dependent modulation of subventricular zone neurogenesis

“…At the end of treatments mice were deeply anesthetized with ketamine (100 mg/kg) and medetomidine (1 mg/kg); they were transcardially perfused with an oxygenated Ringer’s solution (pH 7.3), followed by 4% paraformaldehyde (PFA) in 0.1 M PBS (pH 7.4) and brains were collected, post-fixed overnight at 4 °C and then transferred to a solution of 30% sucrose in 0.1 M PBS. Brains were sectioned sagittally (20-μm thick) to better visualize the migration of SVZ neuroblasts to the OB, or coronally (40-μm thick) 6 , 11 , 58 , 59 by a cryostat (SLEE, Mainz, Germany) and sections were stored at −20 °C until use.…”