Site-directed antisense oligonucleotide decreases the expression of amyloid precursor protein and reverses deficits in learning and memory in aged SAMP8 mice
| Autor: | Mark Franko, Vyas Kamlesh, Susan A. Farr, James F. Flood, William A. Banks, Vijaya B. Kumar, John E. Morley |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Time Factors Physiology Transgene Blotting Western Hippocampus Enzyme-Linked Immunosorbent Assay Biochemistry Amygdala Amyloid beta-Protein Precursor Mice Cellular and Molecular Neuroscience Endocrinology Alzheimer Disease Memory Internal medicine mental disorders medicine Amyloid precursor protein Animals Humans Learning RNA Messenger Maze Learning biology Chemistry Oligonucleotide Age Factors P3 peptide Oligonucleotides Antisense Molecular biology Mice Mutant Strains Protein Structure Tertiary Blot medicine.anatomical_structure biology.protein Antibody |
| Zdroj: | Peptides. 21:1769-1775 |
| ISSN: | 0196-9781 |
| Popis: | beta amyloid protein (Abeta) is a 40-43 amino acid peptide derived from amyloid precursor protein (APP). Abeta has been implicated as a cause of Alzheimer's disease (AD). Mice with spontaneous or transgenic overexpression of APP show the histologic hallmarks of AD and have impairments in learning and memory. We tested whether antisense phosphorothiolated oligonucleotides (AO) directed at the Abeta region of the APP gene given with or without antibody directed at Abeta could reverse the elevated protein levels of APP and the behavioral impairments seen in SAMP8 mice, a strain which spontaneously overexpresses APP. We found that intracerebroventricular (ICV) administration of antibody with either of two AOs directed at the midregion of Abeta improved acquisition and retention in a footshock avoidance paradigm, whereas two AOs directed more toward the C-terminal, a random AO, and vehicle were without effect. Three injections of the more potent AO given without antibody reduced APP protein levels by 43-68% in the amygdala, septum, and hippocampus. These results show that AO directed at the Abeta region of APP can reduce APP levels in the brain and reverse deficits in learning and memory. |
| Databáze: | OpenAIRE |
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