Lauterborn J, Berschauer R, Gall C
Department of Anatomy and Neurobiology, University of California, Irvine 92717, USA.
Neuroscience. 1995 Sep;68(2):363-78. doi: 10.1016/0306-4522(95)00150-h.
Reports of glucocorticoid effects on neurotrophin expression suggest that adrenal hormones may contribute to the pattern of changes in the expression of these factors induced by neuronal activity and seizures. To examine this possibility, the present study evaluated the influence of adrenalectomy on basal expression and seizure-induced alterations in levels of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 messenger RNAs in hippocampus, entorhinal cortex, and superficial neocortex. For determination of hormone effects on basal expression, adult male rats were adrenalectomized and killed 10-14 days later with paired adrenal-intact controls. For studies of adrenal steroid involvement in expression following seizure, adrenalectomized and adrenal-intact rats received a seizure-producing lesion of the dentate gyrus hilus. Changes in neurotrophin messenger RNA content were assessed by quantitative in situ hybridization. Adrenalectomy alone had no significant effect on brain-derived neurotrophic factor messenger RNA content but did result in cell-specific decreases in nerve growth factor and neurotrophin-3 messenger RNAs. Nerve growth factor messenger RNA levels were reduced in hippocampal stratum granulosum, entorhinal cortex, and neocortex but not in cells of the hippocampal molecular layers or hilus. With adrenalectomy, neurotrophin-3 messenger RNA was virtually eliminated from CA2 stratum pyramidale, partially reduced in stratum granulosum, but unaffected in neurons of the hippocampal molecular layers or entorhinal cortex. These effects were partially reversed by corticosterone (2 mg/l) supplement to the drinking saline. In experimental-seizure rats, adrenalectomy did not alter the direction or basic pattern of seizure-induced changes in neurotrophin expression but did change the time courses and magnitudes of these effects. In all areas measured, brain-derived neurotrophic factor messenger RNA content was more greatly and persistently elevated by seizure in adrenalectomized as compared with adrenal-intact rats. In contrast, with adrenalectomy seizures induced smaller increases in nerve growth factor messenger RNA content. Adrenalectomy augmented the decrease in neurotrophin-3 messenger RNA induced by seizure in hippocampus but not in entorhinal cortex. These results demonstrate that adrenal hormones play a major role in the regulation of basal nerve growth factor and neurotrophin-3 messenger RNA expression by specific populations of forebrain neurons. Moreover, the adrenal steroids have opposite effects on activity-dependent changes in brain-derived neurotrophic factor and nerve growth factor messenger RNA levels but are not required for the basic pattern of changes in neurotrophin messenger RNA expression elicited by recurrent seizures.
关于糖皮质激素对神经营养因子表达影响的报告表明，肾上腺激素可能参与了由神经元活动和癫痫发作所诱导的这些因子表达变化模式。为了探究这种可能性，本研究评估了肾上腺切除术对海马体、内嗅皮质和浅表新皮质中神经生长因子、脑源性神经营养因子及神经营养因子-3信使核糖核酸的基础表达以及癫痫发作诱导的水平变化的影响。为了确定激素对基础表达的作用，成年雄性大鼠接受肾上腺切除术，并在10 - 14天后处死，同时设置配对的肾上腺完整对照组。为了研究肾上腺类固醇在癫痫发作后表达中的作用，接受肾上腺切除术和肾上腺完整的大鼠接受齿状回门的癫痫发作诱导性损伤。通过定量原位杂交评估神经营养因子信使核糖核酸含量的变化。单独的肾上腺切除术对脑源性神经营养因子信使核糖核酸含量没有显著影响，但确实导致神经生长因子和神经营养因子-3信使核糖核酸在细胞特异性方面减少。神经生长因子信使核糖核酸水平在海马颗粒层、内嗅皮质和新皮质中降低，但在海马分子层或门区的细胞中未降低。肾上腺切除术后，神经营养因子-3信使核糖核酸在CA2锥体层几乎消失，在颗粒层部分减少，但在海马分子层或内嗅皮质的神经元中未受影响。这些影响通过在饮用盐水中补充皮质酮（2毫克/升）而部分逆转。在实验性癫痫发作大鼠中，肾上腺切除术并未改变癫痫发作诱导的神经营养因子表达变化的方向或基本模式，但确实改变了这些影响的时间进程和幅度。在所有测量区域中，与肾上腺完整的大鼠相比，肾上腺切除的大鼠癫痫发作后脑源性神经营养因子信使核糖核酸含量升高幅度更大且持续时间更长。相反，肾上腺切除术后癫痫发作诱导的神经生长因子信使核糖核酸含量增加较小。肾上腺切除术增强了癫痫发作诱导的海马体中神经营养因子-3信使核糖核酸的减少，但在内嗅皮质中未增强。这些结果表明，肾上腺激素在前脑神经元特定群体对基础神经生长因子和神经营养因子-3信使核糖核酸表达的调节中起主要作用。此外，肾上腺类固醇对脑源性神经营养因子和神经生长因子信使核糖核酸水平的活动依赖性变化具有相反的影响，但对于反复癫痫发作引发的神经营养因子信使核糖核酸表达变化的基本模式并非必需。
