Changes in cannabinoid receptor binding and mRNA levels in several brain regions of aged rats
Changes in cannabinoid receptor binding and mRNA levels in several brain regions of aged rats
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DOI：
10.1016/s0925-4439(98)00042-8
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发表时间：
1998-09-30
影响因子：
6.2
通讯作者：
Fernández-Ruiz, JJ
中科院分区：
文献类型：
--
作者：
Berrendero, F;Romero, J;Fernández-Ruiz, JJ
我们最近发现，大麻素受体结合和基因表达显着减少，在锥体外系结构的老年大鼠。本研究旨在分析可能存在的类似的衰老诱导的变化，大麻素受体结合和基因表达的大脑区域以外的锥体外系区域，但也包含一个显着的人口大麻素受体，如小脑，海马结构，边缘和下丘脑核，大脑皮层等。为此，我们分析了大麻素受体结合，使用放射自显影，和大麻素受体mRNA水平，使用原位杂交，在载玻片安装的大脑切片从年轻（3个月大）和老年（12岁以上）大鼠。结果如下。在小脑中，老年大鼠在分子层中表现出大麻素受体结合的显著降低（-33.3%），尽管在颗粒层中没有伴随mRNA水平的变化。在大脑皮层中，在老年大鼠的深层（VI）（-18.3%）中发现了结合的小幅（尽管具有统计学显著性）降低，而在浅层（I）中未发现变化。在小脑的情况下，mRNA水平没有改变大脑皮层层（II-III和V-VI）。海马阿蒙角的不同区域在老年和年轻大鼠中表现出相似的大麻素受体结合水平。有趣的是，老年大鼠的mRNA水平下降幅度较小，但具有统计学显著性（CA 1：-26.1%; CA 2：-21.6%; CA 3：-14.4%）。这在另一种海马结构（齿状回）中也观察到（-14.6%），尽管老年大鼠该区域的结合水平增加（+28.4%）。两个下丘脑结构，弓状核和下丘脑腹内侧核，表现出减少大麻素受体结合在老年大鼠（分别为-31.1%和-30.3%），但这是没有看到在内侧视前区。这是伴随着下丘脑腹内侧核的mRNA水平没有变化。在边缘结构中，老年大鼠表现出与年轻大鼠相似的结合水平。这种现象见于延髓核、隔核和基底外侧杏仁核。然而，基底外侧杏仁核中的mRNA水平略有下降（-13.4%），而隔核中的mRNA水平没有改变。最后，其他大脑结构，如中央灰质和脑干，在老年和年轻大鼠中表现出相似的结合水平。然而，值得注意的是，在老年大鼠的脑干中，mRNA水平显著增加（+211.2%），而在年轻大鼠中，该区域的结合水平和mRNA水平非常低。这一显着的增加可能与在该地区的胶质细胞的存在增加，如所揭示的增加在老年大鼠的脑干中观察到的胶质细胞酸性蛋白的免疫反应性相比，年轻animals.In总结，衰老与大麻素受体在小脑，大脑皮层，边缘系统和下丘脑结构，海马和其他脑区的变化。然而，观察到的变化（i）并不像早期报告的锥体外系区那样显著和相关，（ii）表现出区域差异，这可能归因于这些受体在每个区域发挥的不同作用。特别相关的幅度是在小脑和下丘脑中发现的衰老诱导的结合减少，以及在脑干中观察到的mRNA水平增加。后者可能与可能含有大麻素受体mRNA的神经胶质细胞的存在增加有关。(C)1998 Elsevier Science B. V.保留所有权利。
We have recently found that cannabinoid receptor binding and gene expression markedly decreased in extrapyramidal structures of aged rats. The present study was designed to analyze the possible existence of similar aging-induced changes in cannabinoid receptor binding and gene expression in brain regions other than extrapyramidal areas, but that also contain a significant population of cannabinoid receptors, such as the cerebellum, hippocampal structures, limbic and hypothalamic nuclei, the cerebral cortex and others. To this end, we analyzed cannabinoid receptor binding, using autoradiography, and cannabinoid receptor mRNA levels, using in situ hybridization, in slide-mounted brain sections obtained from young (3 month old) and aged (greater-than 2 year old) rats. Results were as follows. In the cerebellum aged rats exhibited a marked decrease in cannabinoid receptor binding in the molecular layer (-33.3%), although accompanied by no changes in mRNA levels in the granular layer. In the cerebral cortex, a small, although statistically significant, decrease in binding was found in the deep layer (VI) (-18.3%)of aged rats, whereas no changes were found in the superficial layer (I). As in the case of the cerebellum, mRNA levels did not change in the cerebral cortex layers (II-III and V-VI). The different regions of the Ammon's horn of the hippocampus exhibited similar cannabinoid receptor binding levels in aged and young rats. Interestingly, mRNA levels decreased in aged rats to a small, but statistically significant, extent (CA1: -26.1%; CA2: -21.6%; CA3: -14.4%). This was also seen in another hippocampal structure, the dentate gyrus (-14.6%), although in this region binding levels increased in aged rats (+28.4%). Two hypothalamic structures, the arcuate nucleus and the ventromedial hypothalamic nucleus, exhibited decreased cannabinoid receptor binding in aged rats (-31.1% and -30.3%, respectively), but this was not seen in the medial preoptic area. This was accompanied by no changes in mRNA levels in the ventromedial hypothalamic nucleus. In the limbic structures, aged rats exhibited similar binding levels to young rats. This was seen in the nucleus accumbens, septum nuclei and basolateral amygdaloid nucleus. However, mRNA levels slightly decreased in the basolateral amygdaloid nucleus (-13.4%), whereas they were not altered in the septum nuclei. Finally, other brain structures, such as the central gray substance and the brainstem, exhibited similar binding levels in aged and young rats. However, it is important to note that mRNA levels increased significantly (+211.2%) in the brainstem of aged rats, an area where the levels of binding and mRNA were very low in young rats. This marked increase may be related to an increase in the presence of glial elements in this region, as revealed by the increase in the immunoreactivity for glial fibrillary acidic protein observed in the brainstem of aged rats as compared to young animals.In summary, senescence was associated with changes in cannabinoid receptors in the cerebellum, the cerebral cortex, limbic and hypothalamic structures, the hippocampus and other brain regions. However, the changes observed (i) were not as marked and relevant as those early reported in extrapyramidal areas, and (ii) exhibited regional differences that might be attributed to the different roles played by these receptors in each region. Of particular relevance by their magnitude were the aging-induced decrease in binding found in the cerebellum and the hypothalamus, and the increase in mRNA levels observed in the brainstem. The latter might be related to an increase in the presence of glial cells which might contain cannabinoid receptor mRNA. (C) 1998 Elsevier Science B.V. All rights reserved.