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NEUROTOXICITY OF BETA‐AMYLOID PROTEIN: CYTOCHEMICAL CHANGES AND APOPTOTIC CELL DEATH INVESTIGATED IN ORGANOTYPIC CULTURES
Author(s) -
Allen Y. S.,
Devanathan P. H.,
Owen G. P.
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb02021.x
Subject(s) - neurotoxicity , programmed cell death , apoptosis , immunocytochemistry , dentate gyrus , tunel assay , hippocampal formation , in vitro , amyloid (mycology) , peptide , microbiology and biotechnology , biology , amyloid beta , biochemistry , chemistry , toxicity , neuroscience , endocrinology , botany , organic chemistry
SUMMARY 1. This study is an attempt to examine in vitro the cyto chemical changes in hippocampal neurones induced by beta‐amyloid protein (β‐AP). 2. The mechanism of cell death, and the vulnerability of different regions of the hippocampus to b‐AP toxicity, has also been explored using TUNEL staining to locate fragmented DNA in both dissociated and organotypic cultures. 3. Apoptotic cell profiles and the detection by immunocytochemistry of ubiquitin and tau protein confirmed the acute neurodegenerative effects of b‐AP, and organotypic cultures revealed the dentate gyrus to be especially vulnerable. 4. A scrambled sequence of b‐AP, a peptide with similar hydrophobic groups to b‐AP, and islet pancreatic amyloidogenic peptide also showed neurodegenerative effects, although less severely than b‐AP. 5. It is concluded that organotypic cultures provide a valuable in vitro model with which to observe and characterize the neurotoxic effects of b‐AP. These effects, however, may be non‐specific and related more to the general amyloidogenicity of the b‐AP molecule.