COMPARISON OF NERVE GROWTH-FACTORS EFFECTS ON DEVELOPMENT OF SEPTUM, STRIATUM, AND NUCLEUS BASALIS CHOLINERGIC NEURONS INVITRO
COMPARISON OF NERVE GROWTH-FACTORS EFFECTS ON DEVELOPMENT OF SEPTUM, STRIATUM, AND NUCLEUS BASALIS CHOLINERGIC NEURONS INVITRO
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DOI：
10.1002/jnr.490210227
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发表时间：
1988-10-01
影响因子：
4.2
通讯作者：
HEFTI, F
中科院分区：
文献类型：
--
作者：
HARTIKKA, J;HEFTI, F
在中枢神经系统中，神经生长因子-（NGF）影响发育早期和成年哺乳动物脑中的基底前脑胆碱能神经元。这些神经元位于内侧隔、Broca斜角带和Meynert基底核。虽然神经生长因子对隔胆碱能神经元发育的影响有很好的记录，但对神经生长因子对基底核胆碱能神经元发育的影响知之甚少。除了基底前脑胆碱能神经元外，纹状体中还存在胆碱能中间神经元，其形成解剖学上和功能上不同的胆碱能神经元群体。据报道，这些纹状体中间神经元在早期发育过程中对NGF有反应;然而，目前尚不清楚NGF对其发育的影响是否与隔胆碱能神经元的影响相似。我们准备培养的胎儿大鼠隔，纹状体和基底核的游离细胞，并研究了在存在或不存在NGF的情况下，定位在这三个不同地区的胆碱能神经元的发展。我们现在报告，第一，纹状体和基底核的胆碱能神经元发展更广泛的纤维网络，并含有更多的乙酰胆碱酯酶（AChE）每个神经元比隔胆碱能神经元。每胆碱能神经元的胆碱乙酰转移酶（ChAT）的量是大约相同的，在所有三种培养类型时，生长在没有神经生长因子。第二，神经生长因子治疗增加和抗神经生长因子治疗减少AChE阳性神经元的数量在低平板密度的文化，这表明，神经生长因子是能够促进所有三个领域的胆碱能神经元的生存研究。第三，神经生长因子增加隔培养胆碱能神经元的纤维总长度和分支点的数量，但在纹状体和基底核的文化。第四，神经生长因子治疗增加AChE活性在隔，但不是在基底核或纹状体文化，这表明AChE活性反映了所有领域的胆碱能神经元的纤维网络的程度。第五，神经生长因子治疗产生几倍的升高，在隔培养物中的ChAT活性和更温和的增加，在基底核和纹状体的文化，这表明，神经生长因子是能够刺激ChAT活性，也在没有对生存和纤维生长的刺激作用。我们的研究结果表明，在早期发展，神经生长因子是能够影响所有三个群体的前脑胆碱能神经元的生存和分化。然而，这一发现表明，基底核的胆碱能神经元的形态和它们对NGF的反应不同于隔胆碱能神经元，这表明它们代表功能不同的神经元群体。胆碱能纹状体中间神经元在体外的发展是类似的基底核神经元，这表明在当地环境中的决定因素影响他们的发展命运在原位。据推测，内源性神经生长因子的可用性是参与这些发展决定的决定因素之一。
In the central nervous system, nerve growth factor-(NGF) affects basal forebrain cholinergic neurons during early devleopment and in the adult mammalian brain. These neurons are located in medial septum, diagonal band of Broca, and nucleus basalis of Meynert. While the effects of NGF on the development of septal cholinergic neurons are well documented, only little is known about the influence of NGF on development of cholinergic neurons in the nucleus basalis. In addition to the basal forebrain cholinergic neurons, there are cholinergic interneurons in the corpus striatum, which form an anatomically and functionally distinct population of cholinergic neurons. These striatal interneurons have been reported to respond to NGF during early development; however, it is not known whether the effects of NGF on their development are similar to those on septal cholinergic neurons. We prepared cultures of dissociated cells from fetal rat septum, striatum, and nucleus basalis and investigated the development of cholinergic neurons localized in these three different areas in the presence or absence of NGF. We now report that, first, cholinergic neurons of striatum and nucleus basalis develop a more extensive fiber network and contain more acetylcholinesterase (AChE) per neuron than do cholinergic neurons of septum. The amount of choline acetyltransferase (ChAT) per cholinergic neuron is approximately the same in all three culture types when grown in the absence of NGF. Second, NGF treatment increases and anti-NGF treatment decreases the number of AChE-positive neurons in cultures of low plating density, suggesting that NGF is able to promote survival of cholinergic neurons of all three areas studied. Third, NGF increases the total length of fibers and the number of branching points of cholinergic neurons in septal cultures but not in cultures of striatum and nucleus basalis. Fourth, NGF treatment increases AChE activity in septal but not in nucleus basalis or striatal cultures, suggesting that AChE activity reflects the extent of the fiber network of cholinergic neurons of all areas. Fifth, NGF treatment produces severalfold elevations in ChAT activity in septal cultures and more modest increases in cultures of nucleus basalis and striatum, suggesting that NGF is able to stimulate ChAT activity also in the absence of a stimulatory effect on survival and fiber growth. Our results demonstrate that, during early development, NGF is able to affect survival and differentiation of all three populations of forebrain cholinergic neurons. However, the finding that the morphology of cholinergic neurons of nucleus basalis and their response to NGF differed from those of septal cholinergic neurons suggests that they represent functionally distinct neuronal populations. The development of cholinergic striatal interneurons in vitro was similar to that of nucleus basalis neurons, suggesting that determinants in the local environment influence their developmental fate in situ. It is speculated that the availability of endogenous NGF is one of the determinants involved in these developmental decisions.