Neurobiology Unit, Program in Neurosciences and Institute of Biotechnology and Biomedicine (BIOTECMED), Universitat de València, 46100 Burjassot, Spain.
Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Institute of Experimental Neuroregeneration, Paracelsus Medical University, 5020 Salzburg, Austria.
Int J Mol Sci. 2021 May 27;22(11):5733. doi: 10.3390/ijms22115733.
Immature neurons are maintained in cortical regions of the adult mammalian brain. In rodents, many of these immature neurons can be identified in the piriform cortex based on their high expression of early neuronal markers, such as doublecortin (DCX) and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). This molecule plays critical roles in different neurodevelopmental events. Taking advantage of a DCX-CreERT2/Flox-EGFP reporter mice, we investigated the impact of targeted PSA enzymatic depletion in the piriform cortex on the fate of immature neurons. We report here that the removal of PSA accelerated the final development of immature neurons. This was revealed by a higher frequency of NeuN expression, an increase in the number of cells carrying an axon initial segment (AIS), and an increase in the number of dendrites and dendritic spines on the immature neurons. Taken together, our results demonstrated the crucial role of the PSA moiety in the protracted development of immature neurons residing outside of the neurogenic niches. More studies will be required to understand the intrinsic and extrinsic factors affecting PSA-NCAM expression to understand how the brain regulates the incorporation of these immature neurons to the established neuronal circuits of the adult brain.
不成熟的神经元存在于成年哺乳动物大脑的皮质区域中。在啮齿类动物中,这些不成熟的神经元中的许多可以根据其高水平表达早期神经元标志物,如双皮质素 (DCX) 和神经细胞黏附分子的多聚唾液酸化形式 (PSA-NCAM),在梨状皮层中被识别。该分子在不同的神经发育事件中起着关键作用。利用 DCX-CreERT2/Flox-EGFP 报告小鼠,我们研究了靶向 PSA 酶消耗对梨状皮层中不成熟神经元命运的影响。我们在这里报告,PSA 的去除加速了不成熟神经元的最终发育。这表现在 NeuN 表达的频率更高,携带轴突起始段 (AIS) 的细胞数量增加,以及不成熟神经元的树突和树突棘数量增加。总之,我们的结果表明 PSA 部分在位于神经发生龛外的不成熟神经元的延长发育中起着关键作用。需要进一步研究来了解影响 PSA-NCAM 表达的内在和外在因素,以了解大脑如何调节这些不成熟神经元整合到成年大脑的既定神经元回路中。