LACK OF ALZHEIMER PATHOLOGY AFTER BETA-AMYLOID PROTEIN INJECTIONS IN RAT-BRAIN

被引:129
作者
GAMES, D
KHAN, KM
SORIANO, FG
KEIM, PS
DAVIS, DL
BRYANT, K
LIEBERBURG, I
机构
[1] Athena Neurosciences, South San Francisco
关键词
ALZHEIMERS DISEASE; NEUROTOXICITY; BETA-AMYLOID; CORTEX; HIPPOCAMPUS;
D O I
10.1016/0197-4580(92)90057-5
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
In order to establish a direct relationship between beta-amyloid protein (betaAP) and in vivo neurotoxicity, we made intraparenchymal injections and Alzet pump infusions of betaAP into the hippocampus and cortex of adult rats. We tested a number of synthetic betaAP peptides (betaAP 1-40, 1-38, and 25-35) and peptide controls (scrambled and reversed 1-40, and scrambled and reversed 25-35) over a wide range of concentrations and in a variety of vehicles. The rats were sacrificed from 2-35 days following the implant, and the brains examined by standard immunohistochemical and histological methods used to evaluate the pathologies associated with Alzheimer's disease. We report the lack of Alzheimer related pathology and no significant morphological differences between the betaAP peptide and the peptide and vehicle control injections. These observations indicate that the simple intraparenchymal injection of betaAP in the rat brain is not an appropriate model of Alzheimer-related neurotoxicity.
引用
收藏
页码:569 / 576
页数:8
相关论文
共 28 条
[1]  
AHYMAN BT, 1992, J NEUROPATHOL EXP NE, V51, P76
[2]   NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES [J].
BRAAK, H ;
BRAAK, E .
ACTA NEUROPATHOLOGICA, 1991, 82 (04) :239-259
[3]  
BURDICK D, 1992, J BIOL CHEM, V267, P546
[4]   BETA-AMYLOID INCREASES NEURONAL SUSCEPTIBILITY TO INJURY BY GLUCOSE DEPRIVATION [J].
COPANI, A ;
KOH, JY ;
COTMAN, CW .
NEUROREPORT, 1991, 2 (12) :763-765
[5]  
DAVSON H, 1967, PHYSL CEREBROSPINAL, P41
[6]   EFFECTS OF INJECTED ALZHEIMER BETA-AMYLOID CORES IN RAT-BRAIN [J].
FRAUTSCHY, SA ;
BAIRD, A ;
COLE, GM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (19) :8362-8366
[7]   GOLGI-LIKE DEMONSTRATION OF DARK NEURONS WITH AN ARGYROPHIL-III METHOD FOR EXPERIMENTAL NEUROPATHOLOGY [J].
GALLYAS, F ;
GULDNER, FH ;
ZOLTAY, G ;
WOLFF, JR .
ACTA NEUROPATHOLOGICA, 1990, 79 (06) :620-628
[8]  
KIWALL NW, 1991, P NATL ACAD SCI USA, V88, P7247
[9]   BETA-AMYLOID PROTEIN INCREASES THE VULNERABILITY OF CULTURED CORTICAL-NEURONS TO EXCITOTOXIC DAMAGE [J].
KOH, JY ;
YANG, LL ;
COTMAN, CW .
BRAIN RESEARCH, 1990, 533 (02) :315-320
[10]   AXONAL DISRUPTION AND ABERRANT LOCALIZATION OF TAU-PROTEIN CHARACTERIZE THE NEUROPIL PATHOLOGY OF ALZHEIMERS-DISEASE [J].
KOWALL, NW ;
KOSIK, KS .
ANNALS OF NEUROLOGY, 1987, 22 (05) :639-643