Abstract
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.
Keywords: Amyloid-beta, aging, bryoids, water maze, memory, hippocampus.
Current Alzheimer Research
Title:Acute Oral Bryostatin-1 Administration Improves Learning Deficits in the APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease
Volume: 12 Issue: 1
Author(s): L.M. Schrott, K. Jackson, P. Yi, F. Dietz, G.S. Johnson, T.F. Basting, G. Purdum, T. Tyler, J.D. Rios, T.P. Castor and J.S. Alexander
Affiliation:
Keywords: Amyloid-beta, aging, bryoids, water maze, memory, hippocampus.
Abstract: 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.
Export Options
About this article
Cite this article as:
Schrott L.M., Jackson K., Yi P., Dietz F., Johnson G.S., Basting T.F., Purdum G., Tyler T., Rios J.D., Castor T.P. and Alexander J.S., Acute Oral Bryostatin-1 Administration Improves Learning Deficits in the APP/PS1 Transgenic Mouse Model of Alzheimer’s Disease, Current Alzheimer Research 2015; 12 (1) . https://dx.doi.org/10.2174/1567205012666141218141904
DOI https://dx.doi.org/10.2174/1567205012666141218141904 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A Review on the Antinociceptive Effects of Mitragyna speciosa and Its Derivatives on Animal Model
Current Drug Targets Combining Neuropsychological and Structural Neuroimaging Indicators of Conversion to Alzheimers Disease in Amnestic Mild Cognitive Impairment
Current Alzheimer Research The Amyloid Cascade Hypothesis in Alzheimer’s Disease: It’s Time to Change Our Mind
Current Neuropharmacology Role of Copper in Angiogenesis and Its Medicinal Implications
Current Medicinal Chemistry An Update on Natural Occurrence and Biological Activity of Chromones
Current Medicinal Chemistry Trypsin-Chymotrypsin Inhibitors from Vigna mungo Seeds
Protein & Peptide Letters A Medical Approach to the Monoamine Oxidase Inhibition by Using 7Hbenzo[ e]perimidin-7-one Derivatives
Current Topics in Medicinal Chemistry Taking Down the Unindicted Co-Conspirators of Amyloid β-Peptidemediated Neuronal Death: Shared Gene Regulation of BACE1 and APP Genes Interacting with CREB, Fe65 and YY1 Transcription Factors
Current Alzheimer Research DNA Vaccine and the CNS Axonal Regeneration
Current Pharmaceutical Design Anti-Angiogenic Drugs and Biomarkers in Non-Small-Cell Lung Cancer: 'A Hard Days Night'
Current Pharmaceutical Design Angiogenesis and Hypoxia in Glioblastoma: A Focus on Cancer Stem Cells
CNS & Neurological Disorders - Drug Targets Polyphenols: A Nutraceutical Approach Against Diseases
Recent Patents on Food, Nutrition & Agriculture Bioavailability and Pharmaco-therapeutic Potential of Luteolin in Overcoming Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets Acknowledgements to the Reviewers:
CNS & Neurological Disorders - Drug Targets Editorial: Alzheimer's Disease: From Molecular Mechanisms to Psychobiological Perspectives
Current Alzheimer Research Neuregulin1 as Novel Therapy for Heart Failure
Current Pharmaceutical Design Experimental and Computational Studies on the Inhibition of Acetylcholinesterase by Curcumin and Some of its Derivatives
Current Computer-Aided Drug Design Tools in the Design of Therapeutic Drugs for CNS Disorders: An up-to-date Review
Current Molecular Pharmacology The Dopaminergic Dysfunction and Altered Working Memory Performance of Aging Mice Lacking Gamma-synuclein Gene
CNS & Neurological Disorders - Drug Targets Nitric Oxide: Target for Therapeutic Strategies in Alzheimers Disease
Current Pharmaceutical Design