Acute Oral Bryostatin-1 Administration Improves Learning Deficits in the APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease
| Autor: | T.F. Basting, Lisa M. Schrott, Geoffrey E. Purdum, J. S. Alexander, G.S. Johnson, Theodore A. Tyler, F. Dietz, J.D. Rios, Kasey L. Jackson, Trevor Percival Castor, Ping Yi |
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| Rok vydání: | 2015 |
| Předmět: |
Genetically modified mouse
Bryostatin 1 Administration Oral Morris water navigation task Mice Transgenic Disease Water maze Pharmacology Amyloid beta-Protein Precursor Mice Adjuvants Immunologic Alzheimer Disease Escape Reaction Presenilin-1 Reaction Time Animals Humans Maze Learning Learning Disabilities Cognition Bryostatins Disease Models Animal Orally active Neurology Mutation Neurology (clinical) Psychology Neuroscience |
| Zdroj: | Current Alzheimer Research. 12:22-31 |
| ISSN: | 1567-2050 |
| Popis: | Background: Previous studies showed that Bryostatin-1, a potent PKC modulator and alphasecretase 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 APPswe, 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. |
| Databáze: | OpenAIRE |
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