Van Staveren Wilma C G, Steinbusch Harry W M, Markerink-Van Ittersum Marjanne, Repaske David R, Goy Michael F, Kotera Jun, Omori Kenji, Beavo Joseph A, De Vente Jan
Department of Psychiatry and Neuropsychology, Division Cellular Neuroscience, Maastricht University, European Graduate School of Neuroscience (EURON), 6200 MD Maastricht, The Netherlands.
J Comp Neurol. 2003 Dec 22;467(4):566-80. doi: 10.1002/cne.10955.
Recent evidence indicates that cGMP plays an important role in neural development and neurotransmission. Since cGMP levels depend critically on the activities of phosphodiesterase (PDE) enzymes, mRNA expression patterns were examined for several key cGMP-hydrolyzing PDEs (type 2 [PDE2], 5 [PDE5], and 9 [PDE9]) in rat brain at defined developmental stages. Riboprobes were used for nonradioactive in situ hybridization on sections derived from embryonic animals at 15 days gestation (E15) and several postnatal stages (P0, P5, P10, P21) until adulthood (3 months). At all stages PDE9 mRNA was present throughout the whole central nervous system, with highest levels observed in cerebellar Purkinje cells, whereas PDE2 and PDE5 mRNA expression was more restricted. Like PDE9, PDE5 mRNA was abundant in cerebellar Purkinje cells, although it was observed only on and after postnatal day 10 in these cells. In other brain regions, PDE5 mRNA expression was minimal, detected in olfactory bulb, cortical layers, and in hippocampus. PDE2 mRNA was distributed more widely, with highest levels in medial habenula, and abundant expression in olfactory bulb, olfactory tubercle, cortex, amygdala, striatum, and hippocampus. Double immunostaining of PDE2, PDE5, or PDE9 mRNAs with the neuronal marker NeuN and the glial cell marker glial fibrillary acidic protein revealed that these mRNAs were predominantly expressed in neuronal cell bodies. Our data indicate that three cGMP-hydrolyzing PDE families have distinct expression patterns, although specific cell types coexpress mRNAs for all three enzymes. Thus, it appears that differential expression of PDE isoforms may provide a mechanism to match cGMP hydrolysis to the functional demands of individual brain regions.
最近的证据表明，环磷酸鸟苷（cGMP）在神经发育和神经传递中起着重要作用。由于cGMP水平严重依赖于磷酸二酯酶（PDE）的活性，因此研究了大鼠大脑在特定发育阶段几种关键的cGMP水解PDE（2型[PDE2]、5型[PDE5]和9型[PDE9]）的mRNA表达模式。使用核糖探针在妊娠15天（E15）的胚胎动物以及几个出生后阶段（P0、P5、P10、P21）直至成年期（3个月）的切片上进行非放射性原位杂交。在所有阶段，PDE9 mRNA在整个中枢神经系统中均有表达，在小脑浦肯野细胞中观察到最高水平，而PDE2和PDE5 mRNA的表达则更为局限。与PDE9一样，PDE5 mRNA在小脑浦肯野细胞中丰富，尽管仅在出生后第10天及之后在这些细胞中观察到。在其他脑区，PDE5 mRNA表达极少，仅在嗅球、皮层和海马体中检测到。PDE2 mRNA分布更广泛，在内侧缰核中水平最高，在嗅球、嗅结节、皮层、杏仁核、纹状体和海马体中大量表达。用神经元标记物NeuN和神经胶质细胞标记物胶质纤维酸性蛋白对PDE2、PDE5或PDE9 mRNA进行双重免疫染色显示，这些mRNA主要在神经元细胞体中表达。我们的数据表明，三个cGMP水解PDE家族具有不同的表达模式，尽管特定细胞类型可同时表达这三种酶的mRNA。因此，PDE同工型的差异表达似乎可能提供一种机制，使cGMP水解与各个脑区的功能需求相匹配。
