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Updated: Aug 18, 2026
Experience-Dependent Remodeling of Juvenile Brain Olfactory Sensory Neuron Synaptic Connectivity in an Early-Life Critical Period
Published on: March 1, 2024
Temporal profiling of gene expression during neurogenesis and remodeling in the olfactory epithelium at short
Thomas V Getchell1, Hua Liu, Radhika A Vaishnav
1Department of Physiology, University of Kentucky, Lexington, 40536-0230, USA. tgetche@uky.edu
Abstract:
Neurogenesis in the olfactory epithelium (OE) is induced by olfactory bulbectomy (OBX), which effectively axotomizes olfactory sensory neurons (OSNs) and removes their synaptic targets, resulting in apoptosis. We used Affymetrix high-density oligonucleotide arrays to investigate changes in gene expression during initiation of signaling in pathways that regulate apoptosis and neurogenesis in the murine OE at 2, 8, 16, and 48 hr after bilateral OBX compared to that in sham-operated controls. We focused on regulation of a defined set of genes associated with apoptosis, stem/progenitor cell regulation, and cell cycle progression because of the activation of these processes in OE degeneration and remodeling after OBX. After data scrubbing and categorical analysis, one-way analysis of variance identified 72 genes (4.9% of the present known genes) as being regulated significantly (P < 0.05) at one or more points; 50 were defined as regulated differentially with the false discovery rate at 10%. Significant changes in gene expression occurred in all categories as early as 2 hr post-OBX, with the greatest number of differentially regulated genes at 16 and 48 hr. Hierarchical cluster analysis and correlation coefficients were used to identify similarities in patterns of gene expression changes within and across categories. Validation was carried out with SuperArray macroarrays and real-time RT-PCR. Our results confirmed the participation of many genes in known signaling pathways and identified changes in the expression of 42 genes not identified previously as participating in apoptosis and neurogenesis in the OE. Additionally, our analyses indicated the early involvement of genes regulating cytoskeletal reorganization and angiogenesis in the response to OBX. These studies are an important first step in defining early time-dependent changes in gene expression after target ablation that lead to neurogenesis in the olfactory sensory epithelium.
Insights
Olfactory bulbectomy (OBX) triggers neurogenesis in the olfactory epithelium (OE) by altering gene expression. This study reveals early changes in genes regulating apoptosis and stem cell activity following OBX, paving the way for understanding OE regeneration.
Area of Science:
- Neuroscience
- Molecular Biology
- Regenerative Medicine
Background:
- Olfactory bulbectomy (OBX) induces neurogenesis in the olfactory epithelium (OE) by causing apoptosis of olfactory sensory neurons (OSNs).
- Understanding the molecular mechanisms driving OE regeneration after injury is crucial for therapeutic development.
Purpose of the Study:
- To investigate time-dependent gene expression changes in the murine OE following OBX.
- To identify key genes and pathways involved in apoptosis and neurogenesis initiation after OSN axotomy.
Main Methods:
- Gene expression profiling using Affymetrix high-density oligonucleotide arrays at 2, 8, 16, and 48 hours post-OBX.
- Statistical analysis including ANOVA and false discovery rate to identify differentially regulated genes.
- Validation of key findings using SuperArray macroarrays and real-time RT-PCR.
Main Results:
- Significant changes in gene expression were observed as early as 2 hours post-OBX, with the most pronounced changes at 16 and 48 hours.
- 72 genes were significantly regulated, with 50 identified as differentially regulated, including 42 novel genes not previously linked to OE apoptosis and neurogenesis.
- Early involvement of genes regulating cytoskeletal reorganization and angiogenesis was identified.
Conclusions:
- OBX rapidly induces significant, time-dependent changes in gene expression within the OE.
- This study provides a comprehensive early temporal map of gene expression changes critical for OE regeneration.
- Identified novel genes and pathways offer new targets for understanding and promoting olfactory sensory neuron repair.
