| Project/Area Number |
62480190
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
YAMAMURA Yasuhiro Hiroshima Univ Hosp, Hiroshima Univ School of Med, Lecturer, 医学部附属病院, 講師 (10106388)
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| Co-Investigator(Kenkyū-buntansha) |
MIYOSHI Rie Hiroshima Univ School of Med, Assistant, 医学部, 助手 (80209965)
KATAYAMA Sadao Hiroshima Univ Hosp, Hiroshima Univ School of Med, Assistant, 医学部附属病院, 助手 (00211160)
KITO Shozo Hiroshima Univ School of Med, Professor;, 医学部, 教授 (00010140)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Alzheimer disease / basal forebrain nucleus / nerve growth factor / fimbria-fornicotomy / muscarinic acetylcholine receptor / somatostatin receptor / oxotremorine / hippocampus |
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| Research Abstract |
1 Comparative studies on neurotransmitter changes of the human brains of Alzheimer disease and rat-brains with nBM lesion: Our study showed that in the human brains from Alzheimer disease patients the muscarinic-acetylcholine receptors, both the M1- and M2-receptors,were reduced in the CA1 region of the hippocampus. Somatostatin receptor were reduced in number in the cerebral cortex of Alzheimer disease. In the rats with nbM lesions one week prior to the examination, the ipsilateral cerebral cortex showed increased ^3H-QNB binding sites. The observations suggest that the post- as well as presynaptic structures of the cholinergic system are involved in degenerative process of senile dementia of Alzheimer type. Decreased somatostatin receptors in the cerebral cortex of Alzheimen disease indicates the possible role of somatostatin neuron degeneration in this disease.
2 The effect of nerve growth factor on survival of the basal forebrain cholinergic neurons after the fimbria-fornix transsec
… More
tion in rats: Decrease of the number of the medial septal nucl and vertical limb of the diagonal band Broca after fimbria-fornicotomy in rats with intraventricular beta NGF administration could be reduced to 1/4 to 1/5 of the control animal. The fact indicates that the exogenous beta NGF prevents the meuronal death of the basal forebrain cholinergic neurons after fimria-fornicotomy.
3 Localization of the somatostatin receptors in rats studied by in vitro autoradiography: Binding experiments with the use of ^<125>I-Try^<11>-SS-14 showed high densities in the V -VI lay ers and low densities in the I -IV layers of the cerebral cortex, and the highest densities in the rhinal cortex. The olfactory system showed high SS receptor densities. As for the limbic system the CA1 and subiculum had high densities and the pyramidal cell layer had low densities. Among the basal ganglia the caudate-putamen and substantia nigra showed the low and the claustrum the highest receptor densities.
4 Relationship of the muscarinic and somatostatin receptors in rats with intraventricular NGF administration: New born rats of the 2-8th day were injected NGF intraventricularly and the P_2 fraction of the hippocampal tissue was used for the inhibition experiment with oxotremorine /^3 H-H-NMS. The experiments showed a single binding site with the K_i value of 0.46xlO^<-6>, and the the effect of intraventricular NGF administration on mAchR of the hippocampus was the same as that of in vitro SS administration. Application of SS to the hippocampal homogenates made no effects on the inhibition curves. Less
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