Cintra A, Bhatnagar M, Chadi G, Tinner B, Lindberg J, Gustafsson J A, Agnati L F, Fuxe K
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Ann N Y Acad Sci. 1994 Nov 30;746:42-61; discussion 61-3. doi: 10.1111/j.1749-6632.1994.tb39210.x.
A detailed mapping of glucocorticoid receptor (GR) immunoreactivity (IR) in rat CNS was performed employing a mouse monoclonal antibody against rat liver GR. Subjective comparisons were made between the present results and the available data in the literature. A semiquantitation of GR immunostaining was found necessary and was obtained by microdensitometric and morphometric techniques, which enabled the distinction of neuronal and glial cell populations containing GR IR in various CNS regions. GR IR in the CNS was mainly found in the nuclear compartment. The GR was present in neuronal populations with classical neurotransmitters, especially monoamines and glutamate and with various neuropeptides. The degree of colocalization varied according to the function of the brain area. Functional implications were made in relation to stress sensitivity, mood and nociception/antinociception. The global control of networks by glucocorticoids may allow an optimal integration of different types of circuits. The GR is found already in the fetal rat and the development of GR mRNA and receptor protein was followed during the pre- and postnatal periods. The GR appears to be a major factor in brain maturation and in modulation of stress responses. In aged Brown Norway rat brain GR IR but not mineralocorticoid receptor (MR) IR is reduced in the hippocampal nerve cells. The intensity of GR IR but not the number of nerve cells is altered, indicating a reduced activation of the GR in aging in this rat strain. Overall GR participates in neuronal plasticity from fetal and postnatal life to adult life and aging.
利用抗大鼠肝脏糖皮质激素受体(GR)的小鼠单克隆抗体,对大鼠中枢神经系统(CNS)中的GR免疫反应性(IR)进行了详细定位。将本研究结果与文献中的现有数据进行了主观比较。发现有必要对GR免疫染色进行半定量分析,并通过显微密度测定和形态计量技术获得半定量结果,这使得能够区分不同CNS区域中含有GR IR的神经元和胶质细胞群体。CNS中的GR IR主要存在于细胞核中。GR存在于含有经典神经递质的神经元群体中,尤其是单胺类和谷氨酸,以及各种神经肽。共定位程度因脑区功能而异。对压力敏感性、情绪和痛觉/抗痛觉方面的功能意义进行了探讨。糖皮质激素对网络的整体控制可能有助于不同类型回路的最佳整合。在胎鼠中已发现GR,并且在产前和产后期间对GR mRNA和受体蛋白的发育进行了跟踪。GR似乎是脑成熟和应激反应调节中的一个主要因素。在老年棕色挪威大鼠脑中,海马神经细胞中的GR IR降低,但盐皮质激素受体(MR)IR未降低。GR IR的强度改变,但神经细胞数量未改变,表明该大鼠品系衰老过程中GR的激活减少。总体而言,GR参与了从胎儿期、出生后到成年期及衰老过程中的神经元可塑性。