Journal
CURRENT ALZHEIMER RESEARCH
Volume 12, Issue 1, Pages 22-31Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205012666141218141904
Keywords
Amyloid-beta; aging; bryoids; water maze; memory; hippocampus
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Funding
- NIA/NIH SBIR Award: Aphios Corporation 'Alzheimer's Disease Therapeutic' [5R44AG034760]
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Background: Previous studies showed that Bryostatin-1, a potent PKC modulator and alpha-secretase activator, can improve cognition in models of Alzheimer's disease (AD) with chronic (>10 weeks), intraperitoneal (i.p.) administration of the drug. We compared learning and spatial memory in the APP-swe, PSEN1dE985Dbo (APP/PS1) mouse model of AD and studied the ability of acute intraperitoneal and oral Bryostatin-1 to reverse cognitive deficits in this model. Compared to wild-type (WT) mice, APP/PS1 mice showed significant delays in learning the location of a submerged platform in the Morris water maze. Bryostatin-1 was administered over a 2-week course prior to and during water maze testing. Results: Acute i.p. Bryostatin-1 administration did not improve latency to escape but oral Bryostatin-1 significantly improved memory (measured by a reduction in latency to escape). This benefit of oral Bryostatin-1 administration was most apparent during the first 3 days of testing. These findings show that: 1) Bryostatin-1 is orally active in models of learning and memory, 2) this effect can be produced in less than 2 weeks and 3) this effect is not seen with i.p. administration. We conclude that oral Bryostatin-1 represents a novel, potent and long-acting memory enhancer with future clinical applications in the treatment of human AD.
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