Correlations between Water Maze Performance and Cortical Somatostatin mRNA and High‐affinity Binding Sites During Ageing in Rats

Abstract

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.

Minocycline provides protection against β-amyloid(25-35)-induced alterations of the somatostatin signaling pathway in the rat temporal cortex

“…Given the potent amnesic properties reported for A␤(25-35) (Nitta et al, 1994) and the role of SRIF in cognitive processes (Dournaud et al, 1996), the A␤(25-35)-induced reduction in sst density and sst2 expression might be involved in the impairment of cognitive function reported by several laboratories after A␤ administration. The fact that minocycline improves cognition in APP-transgenic mice suggests that this improvement might partly be accounted for by the protective effects of the drug on the SRIF signaling pathway.…”

“…In the temporal cortex, an area involved in cognitive functions, SRIF plays an important role as a neurotransmitter and has been implicated in learning and memory processes (Dournaud et al, 1996). Its biological actions are mediated by receptors belonging to the G-protein-coupled receptor (GPCR) family.…”

Diazepam Attenuation of Somatostatin Binding and Effect of Somatostatin on Accumulation of Inositol 1,4,5-Trisphosphate in the Rat Frontoparietal Cortex

“…SRIF could also reverse the impairment of cognitive functions induced by cysteamine depletion of brain SRIF (Schettini et al 1988). Dournaud et al(1996) suggest that frontal somatostatinergic interneurons are likely to participate in learning behavior and in the regulation of spatial amnesic processes. These authors also suggest that parietal somatostatinergic interneurons are involved in spatial memory processes.…”

“…Nabeshima et al (1990) suggest that benzodiazepines induce disruptive effects on learning and memory through their recognition site on the GABA receptor and that benzodiazepine-induced learning and memory impairment of is, at least in part, the result of the dysfunction of the cholinergic neuronal system. However, because of the important role of brain tetradecapeptide somatostatin (SRIF) in the cognitive functions of rats (Cacabelos et al 1988;Dournaud et al 1996;Matsuoka et al 1994;Schettini et al 1988;Vècsei et al 1984;), and interaction between somatostatinergic and GABAergic neuronal systems (Boyano-Adánez et al 1995;Hendry et al 1984;Kawaguchi and Kubota 1998;Llorens-Cortes et al 1992;Xie and Sastry 1992) it is possible to assume that the somatostatinergic system is implicated in the mechanism of action of diazepam. SRIF is widely distributed in the central nervous system (CNS) and peripheral tissues (see Reichlin 1983).…”

Complementarity of radioautographic and immunohistochemical techniques for localizing neuroreceptors at the light and electron microscopy level

“…sst2A receptors were labeled using tyramide-amplified peroxidase (light microscopy) or immunogold (electron microscopy) techniques with an antibody directed against a specific amino acid sequence located in the C-terminus of the receptor, developed and characterized by Dr. Agnes Schonbrunn, Houston, TX. sst2-binding sites were labeled in vitro by incubation of frozen sections with an iodinated somatostatin analogue ( 125 I-D-Trp8-somatostatin), as described by Dournaud et al (17). Immunohistochemical results were also compared to radioautographic data generated with sst2-preferring radioligands, as reported in the literature (reviewed in 16).…”