Opioid Modulation of Differential Gene Expression and Neuronal Differentiation in the Ventricular-subventricular Zone of Adult Male Zebra Finches.

Background: The endogenous opioid system regulates diverse functions including pain, physiological processes and motivation. An earlier study had demonstrated increased cell proliferation in the neurogenic niche, that is, the ventricular-subventricular zone (V-SVZ) of adult male zebra finches ( Purpose: To explore gene expression changes underlying the increase in cell proliferation in the V-SVZ of these birds after blocking opioid receptors (ORs) with systemic injections of naloxone. To assess whether opioid antagonism influences neuronal differentiation in the V-SVZ adjacent to the song control nuclei HVC and Area X, both critical for song learning and production. Methods: Whole transcriptome microarray analysis of the V-SVZ was performed following naloxone or vehicle administration. The analysis identified 26 differentially expressed transcripts (fold change [FC] ≥ 1.5), including upregulated genes associated with neuroblast migration, neuronal differentiation, synaptic plasticity, and chromatin remodelling. Quantification of bromodeoxyuridine (BrdU) and doublecortin (DCX) positive cells was performed to determine proliferation and neuronal differentiation in the V-SVZ adjacent to HVC and Area X. Results: Among differentially expressed transcripts, Conclusion: Together, these results demonstrate that OR blockade may promote neurogenesis in adult songbirds and is accompanied by the upregulation of key transcripts, including miR-124-3p. Given the established role of miR-124 in promoting neuronal differentiation, its upregulation suggests that OR blockade may enhance neuronal differentiation via microRNA (miRNA)-mediated pathways. This finding provides the first evidence linking opioid modulation to miRNA-driven neurogenic processes in an adult avian brain.