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Published on: February 23, 2014
Changes in cell migration and survival in the olfactory bulb of the pcd/pcd mouse
J Valero1, E Weruaga, A R Murias
1Lab Plasticidad Neuronal y Neurorreparación, Instituto de Neurociencias de Castilla y León, Universidad de Salamanca, E-37007 Salamanca, Spain.
Abstract:
Postnatally, the Purkinje cell degeneration mutant mice lose the main projecting neurons of the main olfactory bulb (OB): mitral cells (MC). In adult animals, progenitor cells from the rostral migratory stream (RMS) differentiate into bulbar interneurons that modulate MC activity. In the present work, we studied changes in proliferation, tangential migration, radial migration patterns, and the survival of these newly generated neurons in this neurodegeneration animal model. The animals were injected with bromodeoxyuridine 2 weeks or 2 months before killing in order to label neuroblast incorporation into the OB and to analyze the survival of these cells after differentiation, respectively. Both the organization and cellular composition of the RMS and the differentiation of the newly generated neurons in the OB were studied using specific markers of glial cells, neuroblasts, and mature neurons. No changes were observed in the cell proliferation rate nor in their tangential migration through the RMS, indicating that migrating neuroblasts are only weakly responsive to the alteration in their target region, the OB. However, the absence of MC does elicit differences in the final destination of the newly generated interneurons. Moreover, the loss of MC also produces changes in the survival of the newly generated interneurons, in accordance with the dramatic decrease in the number of synaptic targets available.
Insights
In Purkinje cell degeneration mutant mice, olfactory bulb interneuron migration is unaffected, but their survival and destination change due to the loss of mitral cells, impacting neurogenesis.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurodegeneration
Background:
- Purkinje cell degeneration (PCD) mutant mice exhibit postnatal loss of olfactory bulb (OB) mitral cells (MC), the primary projecting neurons.
- Adult neurogenesis in the OB involves progenitor cells from the rostral migratory stream (RMS) differentiating into interneurons that modulate MC activity.
Purpose of the Study:
- To investigate alterations in proliferation, migration, and survival of new interneurons in the OB of PCD mutant mice.
- To assess the impact of MC loss on the differentiation and integration of newly generated interneurons.
Main Methods:
- Bromodeoxyuridine (BrdU) labeling to track neuroblast incorporation and survival.
- Immunohistochemistry using markers for glial cells, neuroblasts, and mature neurons.
- Analysis of RMS organization, tangential and radial migration, and neuronal differentiation in the OB.
Main Results:
- Cell proliferation rates and tangential migration through the RMS remained unchanged in PCD mice.
- Migrating neuroblasts showed limited responsiveness to the altered OB environment.
- The absence of MCs led to altered destinations and reduced survival of newly generated interneurons in the OB.
Conclusions:
- Neurogenesis in the RMS is largely independent of the target region's cellular composition.
- The loss of MCs significantly impacts the survival and final positioning of new OB interneurons due to reduced synaptic targets.
