Chao H M, McEwen B S
Rockefeller University, Laboratory of Neuroendocrinology, New York, NY 10021.
Brain Res Mol Brain Res. 1994 Oct;26(1-2):271-6. doi: 10.1016/0169-328x(94)90099-x.
The genes encoding brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and basic fibroblast growth factor (bFGF) are all expressed in the adult rat hippocampus. The colocalization of the these factors with the receptors to which they bind, namely trkB, trkC and the bFGF receptor, respectively, suggests that in the hippocampus they may exert their putative protective and trophic effects through an autocrine mechanism. The morphology and survival of hippocampal neurons are also affected by glucocorticoids, which can act as transcriptional activators of gene expression. In this study we have used in situ hybridization to investigate the adrenal steroid regulation of the mRNAs encoding the neurotrophic factors BDNF, NT-3, and bFGF, their respective receptors, and the growth-associated protein GAP-43. After 7 days of adrenalectomy (ADX), there was an increase in the level of GAP-43 mRNA expression in the CA1 and CA3 pyramidal cell layers of the hippocampus, that was prevented by corticosterone replacement to the ADX animals. In the CA2 subregion, adrenalectomy resulted in a decrease in bFGF mRNA expression, that was reversed by steroid treatment. There was evidence for glucocorticoid modulation of the BDNF and NT-3 mRNAs in pyramidal cell layers and in the dentate gyrus, but not of the mRNAs encoding the trkB, trk C or bFGF receptors.
编码脑源性神经营养因子（BDNF）、神经营养因子-3（NT-3）和碱性成纤维细胞生长因子（bFGF）的基因均在成年大鼠海马体中表达。这些因子分别与其结合的受体（即trkB、trkC和bFGF受体）共定位，这表明在海马体中它们可能通过自分泌机制发挥其假定的保护和营养作用。海马神经元的形态和存活也受到糖皮质激素的影响，糖皮质激素可作为基因表达的转录激活剂。在本研究中，我们使用原位杂交技术来研究肾上腺类固醇对编码神经营养因子BDNF、NT-3和bFGF、它们各自的受体以及生长相关蛋白GAP-43的mRNA的调节作用。肾上腺切除（ADX）7天后，海马体CA1和CA3锥体细胞层中GAP-43 mRNA表达水平升高，而给ADX动物补充皮质酮可阻止这种升高。在CA2亚区域，肾上腺切除导致bFGF mRNA表达下降，而类固醇治疗可使其逆转。有证据表明糖皮质激素对锥体细胞层和齿状回中的BDNF和NT-3 mRNA有调节作用，但对编码trkB、trkC或bFGF受体的mRNA没有调节作用。
