Dournaud P, Jazat-Poindessous F, Slama A, Lamour Y, Epelbaum J
U. 159 INSERM, Centre Paul Broca, Paris, France.
Eur J Neurosci. 1996 Mar;8(3):476-85. doi: 10.1111/j.1460-9568.1996.tb01231.x.
Somatostatin levels and high-affinity (somatostatin-1) binding sites are decreased in post-mortem cortical samples of Alzheimer's disease patients but the relationships between such modifications and the cognitive deficits remain to be established. We investigated these relationships in the ageing rat. Three age groups (3-4, 14-15 and 26-27 months) were tested in a modified version of the Morris water maze. Somatostatin mRNA levels were quantified by in situ hybridization and somatostatin binding sites by radioautography using the selective agonist octreotide (SMS 201995) as a competing drug to evaluate high-affinity (somatostatin-1) and low-affinity (somatostatin-2) binding sites. The number of somatostatin mRNA-containing cells was not modified with age or memory performance in cortical, hippocampal and hypothalamic regions, but somatostatin mRNA densities were significantly decreased with age and with memory performance in the frontal and parietal cortex. In the frontal cortex somatostatin mRNA densities were already decreased in 14- to 15-month-old rats, whereas the decrease was observed only in 26- to 27-month-old rats in the parietal cortex. A decrease in somatostatin-1 binding was observed with memory performance, independently of age, in the basolateral amygdala only, while somatostatin-2 binding sites were not affected. In the frontal and parietal cortex, a significant correlation occurred between the latency to find the invisible platform in the water maze and somatostatin mRNA (r = -0.54 and 0.59 respectively, P < 0.02). These results indicate that ageing rats with memory impairments display some of the features of the somatostatinergic deficits observed in Alzheimer's disease.
在阿尔茨海默病患者的死后皮质样本中，生长抑素水平和高亲和力（生长抑素-1）结合位点减少，但这些改变与认知缺陷之间的关系仍有待确定。我们在衰老大鼠中研究了这些关系。将三个年龄组（3-4个月、14-15个月和26-27个月）的大鼠在改良版的莫里斯水迷宫中进行测试。通过原位杂交对生长抑素mRNA水平进行定量，并使用选择性激动剂奥曲肽（SMS 201995）作为竞争药物，通过放射自显影对生长抑素结合位点进行定量，以评估高亲和力（生长抑素-1）和低亲和力（生长抑素-2）结合位点。在皮质、海马和下丘脑区域，含生长抑素mRNA的细胞数量不会随年龄或记忆表现而改变，但在额叶和顶叶皮质，生长抑素mRNA密度会随年龄和记忆表现显著降低。在额叶皮质，14至15个月大的大鼠中生长抑素mRNA密度就已降低，而在顶叶皮质，仅在26至27个月大的大鼠中观察到这种降低。仅在基底外侧杏仁核中，生长抑素-1结合随记忆表现而降低，与年龄无关，而生长抑素-2结合位点不受影响。在额叶和顶叶皮质，水迷宫中找到不可见平台的潜伏期与生长抑素mRNA之间存在显著相关性（分别为r = -0.54和0.59，P < 0.02）。这些结果表明，有记忆障碍的衰老大鼠表现出了在阿尔茨海默病中观察到的生长抑素能缺陷的一些特征。
