Wanaka A, Carroll S L, Milbrandt J
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Brain Res Dev Brain Res. 1993 Mar 19;72(1):133-44. doi: 10.1016/0165-3806(93)90166-8.
Pleiotrophin (PTN) is a newly identified heparin-binding growth factor which is closely related to the retinoic acid-inducible MK protein. PTN is expressed at high levels in perinatal brain and promotes neurite outgrowth from embryonic brain neurons and mitogenesis in fibroblasts, suggesting that it may play an important role in the development of the nervous system. We have used in situ hybridization to examine PTN expression in the developing and adult rat nervous systems. During embryogenesis, PTN mRNA is primarily expressed by neuroglial progenitor cells in the subependymal layer of the central nervous system (CNS), whereas during the perinatal period high levels of PTN transcripts are found in neurons as well as glial elements (astrocytes and oligodendrocytes). In the adult brain, PTN expression is markedly decreased relative to early postnatal brain and, in contrast to the neuronal and glial expression observed in young animals, is confined to specific neuronal subpopulations (especially hippocampal CA1-3 regions, cerebral cortex laminae II-IV). PTN is also expressed in the developing spinal cord and eye. In the peripheral nervous system (PNS), PTN mRNA is present in ganglionic neurons during embryogenesis. In adult ganglia, however, PTN expression becomes localized to the satellite cells of the ganglia. The developmental pattern of PTN expression in the CNS and the 'switch' in expression from neurons to satellite cells in the PNS suggests that it has important functions not only in the developing nervous system, but also in the adult CNS and PNS and that the functions performed by this growth factor change during ontogeny. We have also found that levels of PTN mRNA are dramatically but transiently elevated in neurons of the hippocampus, piriform cortex and parietal cortex following a chemically induced seizure, indicating that neuronal PTN mRNA expression is increased by intense physiological stimuli and may play a role in the response to these stimuli.
多效生长因子（PTN）是一种新发现的肝素结合生长因子，与视黄酸诱导的MK蛋白密切相关。PTN在围产期大脑中高水平表达，可促进胚胎脑神经元的神经突生长和成纤维细胞的有丝分裂，提示其可能在神经系统发育中发挥重要作用。我们利用原位杂交技术检测了发育中和成年大鼠神经系统中PTN的表达情况。在胚胎发生过程中，PTN mRNA主要由中枢神经系统（CNS）室管膜下层的神经胶质祖细胞表达，而在围产期，神经元以及胶质成分（星形胶质细胞和少突胶质细胞）中可发现高水平的PTN转录本。在成体大脑中，相对于出生后早期大脑，PTN表达明显降低，并且与幼龄动物中观察到的神经元和胶质细胞表达情况不同，PTN局限于特定的神经元亚群（尤其是海马CA1 - 3区、大脑皮层II - IV层）。PTN也在发育中的脊髓和眼睛中表达。在周围神经系统（PNS）中，胚胎发生期间神经节神经元中存在PTN mRNA。然而，在成年神经节中，PTN表达定位于神经节的卫星细胞。PTN在CNS中的发育表达模式以及在PNS中从神经元到卫星细胞的表达“转换”表明，它不仅在发育中的神经系统中具有重要功能，而且在成体CNS和PNS中也具有重要功能，并且这种生长因子在个体发育过程中执行的功能会发生变化。我们还发现，化学诱导癫痫发作后，海马、梨状皮质和顶叶皮质的神经元中PTN mRNA水平急剧但短暂升高，表明强烈的生理刺激可增加神经元PTN mRNA表达，并且其可能在对这些刺激的反应中发挥作用。
