Antibody to amyloid beta protein alleviates impaired acquisition, retention, and memory processing in SAMP8 mice.
SAMP8 (senescence-accelerated mouse, P8 strain) mice overproduce amyloid precursor protein and beta-amyloid and have learning and memory deficits. Preliminary data have indicated that overproduction of beta-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 beta-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 1 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 beta-amyloid antibody injected 48 h 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.
Morley
John E
JE
Geriatric Research, Education, and Clinical Center, VA Medical Center, St. Louis, Missouri 63106, USA. Morley@slu.edu
Farr
Susan A
SA
Flood
James F
JF
D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D012153:Retention, Psychology / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal