Changes in brain somatostatin in memory-deficient rats: comparison with cholinergic markers.
To clarify the functional role of the brain somatostatinergic system in cognitive processes, changes in the performance in passive avoidance and water maze tasks and in brain somatostatin contents were comparatively investigated in young Fischer rats subjected to brain cholinergic and somatostatinergic depletion, and in aged Fischer rats. Lesioning of the nucleus basalis magnocellularis and administration of cysteamine (200 mg/kg, s.c.), a depletor of somatostatin, resulted in significant deficits in passive avoidance, but complete transection of the fimbria-fornix hardly affected the performance in the task. When cognitive performance was assessed in the Morris water maze, lesions of the nucleus basalis magnocellularis and the fimbria-fornix, and administration of cysteamine, significantly impaired the acquisition of navigatory spatial memories of rats. On the other hand, aged rats (24-27 months) showed severe impairments of memory acquisition in both tasks. Neurochemistry measurements showed that lesions of the nucleus basalis magnocellularis produced a selective reduction both in the cortical cholinergic marker choline acetyltransferase and in striatal somatostatin level, whereas lesioning of the fimbria-fornix caused a marked loss of choline acetyltransferase in the hippocampus and posterior cortex, and a significant reduction in hippocampal somatostatin. On the other hand, treatment with cysteamine significantly reduced the contents of somatostatin in all the brain regions examined, but minimally affected choline acetyltransferase activity. However, significant reduction in the striatal choline acetyltransferase activity and elevation in somatostatin content in the frontal cortex were found in aged rats compared with young rats. Taken together, these results strongly suggest that changes in the brain somatostatinergic transmission are involved in the cognitive deficits in the experimental animal models of dementia presently employed. Furthermore, the present comparative study further implies that there are differences in the relative involvement of the cholinergic and somatostatinergic systems in the performance of rats on two different tests of mnemonic function.
Matsuoka
N
N
Basic Research Group, Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Yamazaki
M
M
Yamaguchi
I
I
D000375:Aging / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000378:metabolism*; D003071:Cognition; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D003543:Cysteamine / Q000494:pharmacology; D003704:Dementia / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000503:physiopathology*; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D013004:Somatostatin / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; D013004:Somatostatin; D003543:Cysteamine; D002795:Choline O-Acetyltransferase