Hatanaka H, Tsukui H, Nihonmatsu I
Department of Neuroscience, Mitsubishi-Kasei Institute of Life Sciences, Tokyo, Japan.
Brain Res. 1988 Mar 1;467(1):85-95. doi: 10.1016/0165-3806(88)90069-7.
Nerve growth factor (NGF), a well-characterized target-derived growth factor, has been postulated to promote neuronal differentiation and survival of the basal forebrain cholinergic neurons. In the present paper, we demonstrate that a developmental change in NGF action occurs in postnatal rat basal forebrain cholinergic neurons in culture. Firstly, NGF acts as maturation factor by increasing choline acetyltransferase (ChAT) activity and acts later as a survival factor. In dissociated cell cultures of septal neurons from early postnatal (P1-4) rats, ChAT activities were increased by the addition of NGF. That is, ChAT activities in P1 septal cells cultured for 7 days was increased 4-fold in the presence of NGF at a concentration of 100 ng/ml. However, the number of the acetylcholinesterase (AChE)-positive neurons was not significantly different between these groups. In contrast, septal neurons from P8 to P14 rats showed different responses to NGF. Although the P14 septal neurons in culture for 7 days without NGF lost about half of the ChAT activity during a 7-day cultivation, cells cultured with NGF retained the activity at the initial level. The number of AChE-positive neurons counted in cultures with NGF was much greater than the number without NGF. These results suggest that, during the early postnatal days, the action of NGF on the septal cholinergic neurons in culture changes from induction of ChAT activity to the promotion of cholinergic neuronal cell survival. During this developmental period in vivo, septal neurons are terminating their projections to the hippocampal formation. Similar NGF-regulated changes in cholinergic neurons were observed in cultured postnatal neurons from vertical limb of diagonal band. An analogy has been pointed out between the neuronal death of the basal forebrain cholinergic neurons and a similar neuronal death in senile dementia, especially Alzheimer's type. The work reported here might present a possibility that NGF could play a role in preventing the loss of the basal forebrain cholinergic neurons in this disease.
神经生长因子（NGF）是一种特征明确的靶源性生长因子，据推测它能促进基底前脑胆碱能神经元的分化和存活。在本文中，我们证明了培养的新生大鼠基底前脑胆碱能神经元中NGF的作用存在发育变化。首先，NGF通过增加胆碱乙酰转移酶（ChAT）的活性发挥成熟因子的作用，随后作为存活因子发挥作用。在出生早期（P1-4）大鼠隔区神经元的解离细胞培养物中，添加NGF可增加ChAT活性。也就是说，在浓度为100 ng/ml的NGF存在下，培养7天的P1隔区细胞中的ChAT活性增加了4倍。然而，这些组之间乙酰胆碱酯酶（AChE）阳性神经元的数量没有显著差异。相比之下，P8至P14大鼠的隔区神经元对NGF表现出不同的反应。虽然在无NGF的情况下培养7天的P14隔区神经元在7天培养期间失去了约一半的ChAT活性，但用NGF培养的细胞将活性维持在初始水平。在添加NGF的培养物中计数的AChE阳性神经元数量远多于未添加NGF的培养物中的数量。这些结果表明，在出生后的早期阶段，NGF对培养的隔区胆碱能神经元的作用从诱导ChAT活性转变为促进胆碱能神经元细胞存活。在体内的这个发育阶段，隔区神经元正在终止其向海马结构的投射。在来自斜角带垂直支的培养新生神经元中也观察到了类似的NGF调节的胆碱能神经元变化。有人指出基底前脑胆碱能神经元的神经元死亡与老年痴呆症，尤其是阿尔茨海默病类型中的类似神经元死亡之间存在相似之处。本文报道的工作可能表明NGF在预防这种疾病中基底前脑胆碱能神经元的丧失方面可能发挥作用。
