Prolonged nicotine exposure, via electronic cigarette, selectively increases Bdnf/TrkB transcription, dynorphin peptide levels and OLIG2 in male rat VTA

Different drugs of abuse affect the Central Nervous System (CNS) neuronal networks and reshape the expression of neuroplasticity-related genes in crucial parts of the mesocorticolimbic reward circuitry, such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Recent evidence suggests that neuronal activity and life experience, including repeated drug exposure, can modulate oligodendrogenesis thus altering neuronal myelination. This study aimed to investigate whether the prolonged exposure to nicotine, via electronic cigarettes, affects oligodendrocyte differentiation. Results showed that exposure to nicotine mainstream enhances the expression of OLIG2, a transcription factor essential for oligodendrocyte differentiation, in male rat VTA. This effect was associated with increased mRNA levels of the epigenetic enzyme Kdm6b, which is involved in regulating OLIG2 expression and synaptic plasticity. In the same brain region, nicotine increased Bdnf and TrkB gene expression as well as dynorphin peptide levels, which are positive regulators for oligodendroglial differentiation. Noteworthy, these molecular changes occurred alongside a reduction in neurofilament light levels, suggesting potential axonal remodelling associated with enhanced oligodendrogenesis. No significant changes in investigated parameters were detected in the NAc, thus suggesting that the reported molecular alterations selectively occurred in the VTA. Protein correlation analysis revealed that prolonged nicotine exposure primarily affects neuroplasticity-related protein networks within this area. Overall, these findings suggest that prolonged nicotine exposure, through electronic cigarettes, induces alterations of oligodendrogenesis modulators in the VTA. These molecular changes may impact axonal conduction velocity and reward circuitry connectivity, promoting neuronal adaptations that could be relevant for the development of addictive behaviour.