P2‐199: Intranasal deferoxamine improves radial arm water maze performance in P301L tau transgenic mice
Year: 2009
Type: article
Abstract: Deferoxamine (DFO), given intramuscularly (IM), has previously been shown in a clinical trial to reduce cognitive decline associated with Alzheimer's disease (AD) by 50% over two years. However, due to side effects and difficulty with administration, IM DFO was not further developed for AD. We have recently shown that intranasal (IN) administration is a non-invasive way to target DFO to the central nervous system. In the APP/PS1 mouse model, intranasally administered DFO slowed the progression of memory loss, as measured by Morris water maze (MWM), with no obvious side-effects. Here, we used a battery of behavioral tests to determine whether intranasal DFO may also have beneficial effects in a transgenic tau mouse model (P301L). Intranasal DFO (10% solution) or vehicle was administered to awake P301L mice and wild-type controls three times per week starting at 2.5 months of age. After 4 months of treatment, mice were subjected to a battery of behavioral tests including radial arm water maze (RAWM), Y-maze, elevated plus maze, open field, MWM, and the optomotor visual test (OPT). Wild-type controls had significantly fewer errors and shorter escape latencies than P301L transgenic mice in RAWM, and MWM hidden platform tests. No obvious differences were observed in the elevated plus or open field tests. Transgenic mice performed significantly poorer than wild-type mice in visual tests including MWM visual platform and OPT. Intranasal DFO improved performance over vehicle-treatment in P301L mice as measured by RAWM, where two blocks showed significantly fewer errors in trials 4 and 5. No other significant drug effects were observed. RAWM and MWM tests showed that transgenic mice had significantly poorer performance than wild-type controls. However, these results may have been affected by impaired visual ability of P301L mice. Intranasal treatment with DFO improved performance in the RAWM, which is our most sensitive assay. Because intranasal DFO treatment did not affect visual ability, this suggests a reduction in memory loss of these mice. Biochemical studies are ongoing to determine mechanisms underlying this effect.
Source: Alzheimer s & Dementia
Authors: Jared M. Fine, Daniel Renner, Amanda Baillargeon, Nicole Hoerster, Julian Tokarev, Sam Colton, Ayla Pelleg, Alexander Andrews, Kirsten Sparley, William H. Frey, Leah R. Hanson
Institution: HealthPartners
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2003593174