P4‐125: APP Antisense Reverses Learning and Memory Deficits in Two Mouse Strains of Alzheimer's
Year: 2010
Type: article
Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the central nervous system (CNS). Learning and memory deficits are the hallmark of Alzheimer's disease. Studies have revealed that beta amyloid (Aß) plays a key role in these deficits. Elevated brain levels of Aß lead to oxidative damage in the brain resulting in learning and memory deficits. The SAMP8 mouse has a natural mutation that produces an age-related impairment in learning and memory that is driven by an age-related increase in brain levels of Aß. All of these AD-like characteristics are reversed by administration into the brain of antibody to Aß and antisense oligonucleotide, termed mOL-1 that is directed at amino acids 17-30 of Aß1-42, a region homologous between human and mouse. Here, we tested mOL-1 in SAMP8 mice and Tg2576 mice two models of Alzheimer's disease using both peripheral and central injections. SAMP8 mice were tested in object recognition with a 24 hour delay after tail vein injection. We also tested our mOL-1 in the Tg2576, that overexpresses the human APP gene and have an age-related impairment in learning and memory, elevated brain levels of Aβ, and increased oxidative damage in the hippocampus. We administered mOL-1, intracerebroventricularly (ICV) to 13 month old Tg2576 mice. We tested the mice in T-maze foot shock avoidance. The SAMP8 mice that received a random control antisense spent 39.67% of the time investigating the novel object whereas the mice which received OL-1 spent 59.9% of the time exploring the novel object. The Tg2576 mice treated with mOL-1 took 9.00 ± 0.72 trials to make an avoidance whereas the Tg2576 mice treated with random antisense took 14.50 ± 1.73. The age-matched wild type controls took 10.09 ± 0.66. On the one week retention test the mOL-1 treated Tg2576 mice took 8.73 ± 0.63 to reach criterion 5 avoidances in 6 consecutive trials, the Tg2576 mice that received random antisense took 16.20 ± 2.58 and the wild type controls took 9.00 ± 0.58 trials to reach criterion. The current findings indicate that antisense oligonucleotide can reverse learning and memory impairment produced by Aβ in both strains of mice.
Source: Alzheimer s & Dementia
Institution: Saint Louis University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
OpenAlex ID: W2044595084