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Effect of Presenilin 1 Missense Mutation and Aluminum on Early Neuronal Development of the Mouse Brain
Author(s) -
Fukusho Eriko,
Nakamura Yu,
Kashiwagi Yujiro,
Kudo Takashi,
Tanaka Toshihisa,
Matsumoto Naohiko,
Kida Tomoyuki,
Nakano Yuka,
Shinosaki Kazuhiro,
Takeda Masatoshi
Publication year - 2001
Publication title -
psychogeriatrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 32
eISSN - 1479-8301
pISSN - 1346-3500
DOI - 10.1111/j.1479-8301.2001.tb00007.x
Subject(s) - presenilin , mutation , missense mutation , neurofilament , biology , neuroscience , disease , pathology , medicine , genetics , alzheimer's disease , immunology , gene , immunohistochemistry
Background : The pathology of Alzheimer's disease (AD) has not been fully elucidated. Presenilin 1 (PS1) mutation is one of the major genetic factors of AD, while aluminum is a candidate for the environmental risk factor. Methods : First, we investigated the influence of PS1 mutation on the neuronal development in ‘knock‐in’ mice of PS1 1213T mutation. Next, the effect of prenatal exposure to aluminum on the neuronal development of the knock‐in mice was examined. Results : In the newborns with the mutated PS1 allele, a tendency of delayed neurological development was seen and an abnormal distribution of neurofilaments was found, implying that the PS1 mutation might alter early neuronal development. Intraperitoneal administration of aluminum‐maltol resulted in the increase of aluminum in brain tissues of newborns, and in abnormal distribution of neurofilaments. Furthermore, the PS1 mutation promoted a change in neurofilament distribution induced by exposure to aluminum. Conclusion : Thus, PS1 mutation and aluminum are suggested to affect early neuronal development, as reflected in some aspects of the pathology of AD.