Koh S, Loy R
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, New York 14642.
J Neurosci. 1989 Sep;9(9):2999-0318. doi: 10.1523/JNEUROSCI.09-09-02999.1989.
In order to understand further the role of NGF in the development of NGF-sensitive basal forebrain neurons and their afferent connections to the hippocampus and neocortex, we have used monoclonal antibody 192 IgG to detect and localize NGF receptors immunocytochemically in the developing rat brain. NGF receptor immunoreactivity (NGF-RI) is first visible at embryonic day 13 (E 13) in the ventrolateral telencephalic wall and follows a caudal-to-rostral gradient in its initial appearance. NGF-RI neuronal number and neuropil staining undergo substantial increases before birth, and extensive dendritic growth and increases in perikaryal size continue during the first 3 weeks of postnatal life. This growth and cellular differentiation, however, is followed in the fourth postnatal week and later by an apparent decrease in dendritic arborization and 50% shrinkage in the size of perikarya. Initial NGF-RI fiber outgrowth from immature basal forebrain neurons directed toward appropriate target fields is observed as early as E 15. The formation of a laminar pattern by septal axons in the hippocampal terminal fields and invasion of NB afferents into the cortex occur postnatally over a protracted time. In the hippocampus, NGF-RI is initially diffusely distributed, and wide bands of immature granule and pyramidal cells are almost devoid of immunoreactive fibers; however, with maturity, septal axon terminals become concentrated in narrow zones closely associated with the cellular layers. In the neocortex, early-arriving basal forebrain afferents accumulate in the intermediate zone underneath the darkly immunoreactive subplate before they enter The cortex. Dense subplate and transiently present, radially aligned fiber staining completely disappear in later postnatal week and are gradually replaced by specific axonal and terminal staining associated with NB afferents. The expression of NGF receptor in the subplate zone at the time afferents arrive and its subsequent disappearance with the specific terminal formation suggest that NGF receptor and concomitant accumulation of NGF in the subplate may act as a temporary target for the early-arriving basal forebrain afferents; ingrowing afferents may then be guided by radially oriented NGF-RI fibers to proper synaptic sites.
为了进一步了解神经生长因子（NGF）在对NGF敏感的基底前脑神经元发育及其与海马体和新皮质传入连接中的作用，我们使用单克隆抗体192 IgG通过免疫细胞化学方法在发育中的大鼠脑中检测和定位NGF受体。NGF受体免疫反应性（NGF-RI）最早在胚胎第13天（E13）出现在腹外侧端脑壁，其最初出现呈尾端到头端的梯度分布。在出生前，NGF-RI神经元数量和神经纤维网染色显著增加，在出生后的前3周，树突广泛生长且胞体大小增加仍在继续。然而，在出生后的第四周及以后，树突分支明显减少，胞体大小缩小50%。早在E15时就观察到来自未成熟基底前脑神经元的初始NGF-RI纤维向适当靶区生长。隔区轴突在海马终末区形成分层模式以及新皮质传入纤维侵入皮质在出生后需要很长时间。在海马体中，NGF-RI最初呈弥散分布，不成熟的颗粒细胞和锥体细胞宽带几乎没有免疫反应性纤维；然而，随着成熟，隔区轴突终末集中在与细胞层紧密相关的狭窄区域。在新皮质中，早期到达的基底前脑传入纤维在进入皮质之前积聚在深色免疫反应性亚板下方的中间区。密集的亚板和短暂出现的、呈放射状排列的纤维染色在出生后后期完全消失，并逐渐被与新皮质传入纤维相关的特定轴突和终末染色所取代。传入纤维到达时亚板区NGF受体的表达及其随后随着特定终末形成而消失表明，NGF受体以及亚板中NGF的伴随积累可能作为早期到达的基底前脑传入纤维的临时靶标；然后，向内生长的传入纤维可能由放射状排列的NGF-RI纤维引导至适当的突触部位。
