Recent results indicate that STriatal-Enriched protein tyrosine Phosphatase (STEP) levels are regulated by brain-derived neurotrophic factor (BDNF), whose expression changes during postnatal development and aging. Here, we studied STEP ontogeny in mouse brain and changes in STEP with age with emphasis on the possible regulation by BDNF. We found that STEP expression increased during the first weeks of life, reaching adult levels by 2–3 weeks of age in the striatum and cortex, and by postnatal day (P) 7 in the hippocampus. STEP protein levels were unaffected in BDNF^+/− mice, but were significantly reduced in the striatum and cortex, but not in the hippocampus, of BDNF^−/− mice at P7 and P14. In adult wild-type mice there were no changes in cortical and hippocampal STEP₆₁ levels with age. Conversely, striatal STEP levels were reduced from 12 months of age, correlating with higher ubiquitination and increased BDNF content and signaling. Lower STEP levels in older mice were paralleled by increased phosphorylation of its substrates. Since altered STEP levels are involved in cellular malfunctioning events, its reduction in the striatum with increasing age should encourage future studies of how this imbalance might participate in the aging process.

最近的结果表明，富含脑纹状体的蛋白质酪氨酸磷酸酶（STEP）的水平受脑源性神经营养因子（BDNF）的调节，其表达在产后发育和衰老过程中会发生变化。在这里，我们研究了小鼠大脑中的STEP个体发育以及STEP随年龄的变化，重点研究了BDNF可能的调控作用。我们发现，STEP的表达在生命的最初几周增加，在纹状体和皮质中达到2–3周龄时达到成人水平，在海马体中达到出生后第7天。STEP蛋白水平在BDNF ^+/-小鼠中不受影响，但在P7和P14时在BDNF ^-/-小鼠的纹状体和皮质中显着降低，但在海马中却没有显着降低。在成年野生型小鼠中，皮层和海马体无变化STEP ₆₁随着年龄的增长。相反，纹状体STEP水平从12个月大时开始降低，这与泛素化程度较高以及BDNF含量和信号转导升高有关。老年小鼠中较低的STEP水平与其底物的磷酸化水平升高相平行。由于STEP水平的改变与细胞功能异常事件有关，因此随着年龄的增长纹状体的减少应鼓励对这种失衡如何参与衰老过程的进一步研究。