Effects of levetiracetam treatment on cognitive and noncognitive impairments in a mouse model of tauopathy

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is characterized clinically by progressive cognitive decline, eventually resulting in death, usually within 10 years of diagnosis. Abnormal tau hyperphosphorylation and its accumulation into neurofibrillary tangles are linked to neurodegeneration in Alzheimer’s disease and similar tauopathies. Aberrant motor behaviors such as pacing/wandering are common in AD. Some AD cases have metabolic changes resulting in weight loss in spite of increased food consumption. Tg4510 mice are characterized by tau deposition in the brain together with cognitive and non‐cognitive impairments that resemble those seen in patients. Leviteracetam is an FDA approved drug that has shown cognitive improvements in mice models of amyloid deposition. The aim of this study was to test the effects of a Leviteracetam diet on cognitive and non‐cognitive impairments in a mouse model of tauopathy, the Tg4510 mice.MethodThree‐month old Tg4510 transgenic and non‐transgenic littermate mice were equally randomly assigned to treated (food containing 240mg/kg Levetiracetam) or placebo (normal diet) groups (n=10, 5F & 5M). All mice were single housed, and food intake and mice body weight were recorded once a week for 3 months. During the last 2 weeks before tissue collection the following behavioral tests were performed: open field, Y‐maze, marble burying, RAWM with reversal, rotarod, novel object recognition (NOR) and fear conditioning. On the last day, the brain was dissected, blood sample was collected, and muscle mass, white fat, and brown fat were weighed.ResultTreatment with Leviteracetam did not improve cognition or activity in Tg4510 during RAWM, open field, and fear conditioning tests. Although Leviteracetam improved performance during rotarod and reduced body weight in non‐transgenic littermates, such effects were not seen in Tg4510 mice.ConclusionThere were no significant improvements in cognitive and non‐cognitive deficits in Tg4510 mice treated with Levetiracetam. Interestingly, Leviteracetam diet resulted in a decrease in body weight together with improvement in rotarod in non‐transgenic littermates when compared to chow diet, whereas no effects were observed in Tg4510 mice treated with leviteracetam. Biochemical and histochemical analysis will be performed in brain tissue to know if treatment with Levetiracetam had an effect on tau pathology.