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Biomedical subjects
Publications and source records attributed to L Bergström.
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We have characterized somatostatinergic phenotype markers of the human neuroblastoma, LA-N-2. A single mRNA-transcript (approximately 850bp) and two cellular somatostatin immunoreactivity forms, a high molecular weight form (M(r) 15,000) and a fragment corresponding to somatostatin-28 was found, while the somatostatin-14 peptide was absent. Saturation binding experiments demonstrated a single class of high-affinity somatostatin receptors with Kd and Bmax of 0.27 +/- 0.03 nM and 45 +/- 1 fmol/mg protein. Partial G-protein uncoupling (30%) was demonstrated, using GTP gamma S, with an affinity of 9.7 nM. The LA-N-2 cell line, previously shown to be cholinergic, may serve as a simplified system to elucidate heterologous neurotransmittor interactions. Such studies are of interest since dysfunctions of the cholinergic basal forebrain neurons and somatostatin immunoreactive interneurons have been consistently observed in Alzheimer's disease.
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We have previously reported increased somatostatin levels in the cerebral cortex of rats housed in impoverished environment and subsequently subjected to a behavioural testing procedure, consisting of open-field exposure and spatial learning. The aim of the present study was to evaluate the degree of neurochemical specificity of the activation of somatostatin neurotransmission and to examine whether the altered levels were due to learning stimulation. Adult rats, previously housed individually for 30 days, were exposed to repeated sessions of a spatial learning task (2 days or 14 days) or repeated sessions of free swimming (14 days). The training sessions of the 14 day group consisted in recurrently changed position of the platform in a learning-set paradigm. Our data showed increased somatostatin immunoreactivity, and unchanged substance P immunoreactivity in the posterior part of the cerebral cortex. However, somatostatin levels increased to a similar extent following 14 days of repeated spatial learning sessions as free swimming sessions. We conclude that the activity of the cortical somatostatin system appears to be sensitive to environmentally induced sensorimotor stimulation in general, rather than learning per se. Thus, external stimulation of early clinical dementia patients with preserved sensorimotor receptivity, in an attempt to restore cognitive function, might be associated with altered somatostatin levels.
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The aim of the present study was to examine the effect of normal aging on somatostatin neurotransmission. Somatostatin gene expression was analysed in several regions of the cerebral cortex and hippocampus in 3, 7 and 21 month-old Sprague-Dawley rats using quantitative in situ hybridization with a 48mer oligodeoxynucleotide antisense probe. Furthermore the distribution of 125I-Tyr11 somatostatin receptor binding sites was studied using quantitative receptor autoradiography. The results demonstrated a significant reduction of preprosomatostatin-mRNA in the frontal cortex of the aged (21 month) group compared with the young (3 month) and the middle-aged (7 month) groups. The receptor binding densities of the aged (21 month) group tended to be lower, compared to the other groups although no significant region-specific changes were evident. These results indicate neurochemical changes in somatostatin-containing neurons in the frontal cortex during aging.