Single and chronic administration of cellulose ethers rescue memory deficit in a transgenic mouse model of Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is an incurable neurodegenerative disease and the major cause of dementia. Recent studies including our findings showed that cellulose ethers (CEs) derivative (TC‐5RW) treatment as a single subcutaneous (SC) dose (4g/kg) have therapeutic effects in neurodegenerative diseases via inhibiting the aggregation of misfolded proteins such as prions and amyloid beta (Aβ). CEs are approved by the FDA as safe, inactive ingredients in foods and pharmaceuticals. Therefore, in this study we aimed to test whether single and repeated treatment with the CE TC‐5RW improves cognitive functions in an animal model of AD.MethodsWe used the 5xFAD mouse model, which harbours five familial AD mutations. The 5xFAD mice co‐overexpress human amyloid precursor protein and presenilin‐1, resulting in overproduction of Aβ and memory deficit. At the age of 6 weeks, one group of 5xFAD mice was treated with a single dose of TC‐5RW (4g/kg/SC) while another group of mice was treated weekly with TC‐5RW (4g/kg/SC) until 7 months of age. Two other groups of mice, wild type (WT) of same background and non‐treated 5xFAD mice were included as controls in our experiment. After completion of TC‐5RW treatment, behavioral studies (novel object recognition (NOR), Y‐maze and contextual fear conditioning (CFC) tests) were performed.ResultsIn the NOR and Y‐maze tests, we observed a reduced percentage of recognition index and spontaneous alteration behavior in 5xFAD mice compared to WT mice. The TC‐5RW treatment at single and chronic dosage significantly increased the percentage of recognition index and spontaneous alteration behavior in 5xFAD mice compared to non‐treated 5xFAD mice. Similarly, the CFC test results showed a lower percentage of time freezing in 5xFAD mice compared to WT mice. Interestingly, TC‐5RW at both dosage regimen significantly improved the percentage of time freezing in 5xFAD mice compared to non‐treated 5xFAD mice.ConclusionIn summary, single and chronic administration of TC‐5RW induce beneficial effects via improving learning and memory functions of 5xFAD mice. These results demonstrate that CE based compounds might be valuable and emerging therapeutics for the prevention and treatment of AD.