Roback J D, Diede S J, Downen M, Lee H J, Kwon J, Large T H, Otten U, Wainer B H
Department of Pathology, University of Chicago, IL 60637.
Brain Res Dev Brain Res. 1992 Nov 20;70(1):123-33. doi: 10.1016/0165-3806(92)90110-i.
Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are members of a family of trophic factors designated the neurotrophins, each of which can bind to the low-affinity NGF receptor (LNGFR). To investigate the mechanisms that regulate the expression of the neurotrophins and the LNGFR in the developing brain, we grew cells from the embryonic mouse septum and hippocampus in reaggregating cell culture and compared neurotrophin and LNGFR expression in developing reaggregates with that seen in the developing septum and hippocampus in situ. NGF, BDNF, NT-3 and LNGFR were each expressed in septal and hippocampal reaggregates as well as the native septum and hippocampus. Additionally, the temporal expression profiles observed in reaggregates were generally similar to those seen in the respective brain regions in situ. In order to determine whether NGF can modulate neurotrophin or LNGFR expression, reaggregates were cultured in the continual presence of either exogenous NGF or anti-NGF antibodies. NGF-treated septal cultures expressed twice the level of LNGFR mRNA as was seen in untreated septal cultures; on the other hand, septal cultures grown in the presence of anti-NGF antibodies, to neutralize endogenously synthesized NGF, displayed a 3-fold decrease in LNGFR mRNA expression compared to untreated cultures. No effects of NGF or anti-NGF were observed on LNGFR expression in hippocampal reaggregates, or on neurotrophin mRNA expression in either reaggregate type. These results suggest that regulatory mechanisms intrinsic to the septal and hippocampal regions control neurotrophin and LNGFR expression. NGF is likely to be one of these regulatory cues since it acts locally in septal reaggregates to control the developmental expression of LNGFR mRNA. The possible roles of locally synthesized NGF and other neurotrophins in the development of septal neurons are discussed.
神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养素-3（NT-3）是一类被称为神经营养因子的营养因子家族成员，它们各自都能与低亲和力NGF受体（LNGFR）结合。为了研究在发育中的大脑中调节神经营养因子和LNGFR表达的机制，我们在重聚集细胞培养中培养了来自胚胎小鼠中隔和海马体的细胞，并将发育中的重聚集体中的神经营养因子和LNGFR表达与发育中的中隔和海马体原位的表达进行了比较。NGF、BDNF、NT-3和LNGFR在中隔和海马体重聚集体以及天然的中隔和海马体中均有表达。此外，在重聚集体中观察到的时间表达谱通常与在相应脑区原位观察到的相似。为了确定NGF是否能调节神经营养因子或LNGFR的表达，重聚集体在持续存在外源性NGF或抗NGF抗体的情况下进行培养。用NGF处理的中隔培养物中LNGFR mRNA的表达水平是未处理中隔培养物的两倍；另一方面，在抗NGF抗体存在下生长的中隔培养物，以中和内源性合成的NGF，与未处理的培养物相比，LNGFR mRNA表达下降了3倍。在海马体重聚集体中未观察到NGF或抗NGF对LNGFR表达的影响，也未观察到对任何一种重聚集体类型中神经营养因子mRNA表达的影响。这些结果表明，中隔和海马体区域固有的调节机制控制着神经营养因子和LNGFR的表达。NGF可能是这些调节信号之一，因为它在中隔重聚集体中局部起作用，以控制LNGFR mRNA的发育表达。讨论了局部合成的NGF和其他神经营养因子在中隔神经元发育中的可能作用。
