Antibody to amyloid β protein alleviates impaired acquisition, retention, and memory processing in SAMP8 mice

被引:86
作者
Morley, JE
Farr, SA
Flood, JF
机构
[1] St Louis Univ, Sch Med, Dept Internal Med, Div Geriatr Med, St Louis, MO 63104 USA
[2] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO 63125 USA
关键词
D O I
10.1006/nlme.2001.4047
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
SAMP8 (senescence-accelerated mouse, P8 strain) mice overproduce amyloid precursor protein and 8-amyloid and have learning and memory deficits. Preliminary data have indicated that overproduction of B-amyloid plays a role in the pathogenesis of acquisition and retention deficits in SAMP8 mice. In the studies reported here, the authors examined the effects of polyclonal and monoclonal antibodies to 8-amyloid on acquisition and retention in an aversive T-maze testing paradigm when injected intracerebroventricularly (ICV) into 12-month SAMP8/TaJF mice. Both the polyclonal and monoclonal antibodies improved acquisition and retention when injected ICV I to 14 days prior to acquisition testing. Injection of all three antibodies intrahippocampally immediately following training improved retention on the T-maze when mice were tested 7 days later. The authors next studied the effect of monoclonal 8-amyloid antibody injected 48 It prior to training on the effect on retention in the T-maze of drugs modulating classical neurotransmitters. Arecoline and glutamate were injected directly into the hippocampus, and ketanserin, methiothepen, bicuculline, and OH-saclofen were injected into the septum. Previously, the authors have found that the doses of these drugs required to improve retention are markedly altered in 12-month SAMP8/TkJF mice compared to 4-month P8 mice. In these studies, it was demonstrated that antibody to beta-amyloid resulted in these drugs improving retention at doses that improved memory in 4-month SAMP8/TaJF mice. Based on these findings, we conclude that beta-amyloid overproduction is at least in part responsible for the acquisition and memory deficits in 12-month-old SAMP8/TaJF mice. Antibody to beta-amyloid restores the retention response to neurotransmitter manipulation to that seen in 4-month-old mice. beta-amyloid appears to play a key role in the loss of acquisition and retention seen in SAMP8/TaJF mice.
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页码:125 / 138
页数:14
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