Holtzman D M, Lee S, Li Y, Chua-Couzens J, Xia H, Bredt D S, Mobley W C
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Neurochem Res. 1996 Jul;21(7):861-8. doi: 10.1007/BF02532310.
Nerve growth factor (NGF) acts through the receptor tyrosine kinase trkA to serve as a trophic factor for cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band. We have previously shown that the neuronal isoform of nitric oxide synthase (NOS) is selectively expressed in a large fraction of trkA-expressing cholinergic neurons in these brain regions in the adult rat, and that NGF induces the expression of neuronal-NOS in these cells. Herein, we show that: 1) neuronal-NOS is also localized to these neurons in the developing septum; 2) the expression of neuronal-NOS is regulated in the developing medial septal nucleus and vertical limb of the diagonal band; 3) neuronal-NOS regulation parallels that for other markers of basal forebrain cholinergic neuron differentiation, such as cholineacetyltransferase; and 4) NGF infusion in the postnatal period induces robust increases in neuronal-NOS mRNA and in NOS activity in the basal forebrain. Taken together with earlier findings, our results suggest that neuronal-NOS has a role in the differentiation and mature function of septal cholinergic neurons. Through enhancing neuronal-NOS synthesis, endogenous NGF is likely to regulate NO functions in vivo.
神经生长因子（NGF）通过受体酪氨酸激酶trkA发挥作用，作为内侧隔核和斜角带垂直支中胆碱能神经元的营养因子。我们之前已经表明，一氧化氮合酶（NOS）的神经元同工型在成年大鼠这些脑区中大部分表达trkA的胆碱能神经元中选择性表达，并且NGF可诱导这些细胞中神经元型NOS的表达。在此，我们表明：1）神经元型NOS在发育中的隔区这些神经元中也有定位；2）神经元型NOS的表达在发育中的内侧隔核和斜角带垂直支中受到调节；3）神经元型NOS的调节与基底前脑胆碱能神经元分化的其他标志物（如胆碱乙酰转移酶）的调节相似；4）出生后时期注入NGF可诱导基底前脑神经元型NOS mRNA和NOS活性显著增加。结合早期研究结果，我们的结果表明神经元型NOS在隔区胆碱能神经元的分化和成熟功能中起作用。通过增强神经元型NOS的合成，内源性NGF可能在体内调节NO的功能。
