Chronic ramelteon treatment in a mouse model of Alzheimer's disease.

TitleChronic ramelteon treatment in a mouse model of Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2012
AuthorsMcKenna JTimothy, Christie MA, Jeffrey BA, McCoy JG, Lee E, Connolly NP, Ward CP, Strecker RE
JournalArch Ital Biol
Date Published2012 Mar
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Antipsychotic Agents, Apoptosis, Brain, Cognition Disorders, Disease Models, Animal, Follow-Up Studies, Humans, Indenes, Maze Learning, Mice, Mice, Transgenic, Mutation, Plaque, Amyloid, Poly(ADP-ribose) Polymerases, Presenilin-1, Time Factors

Prior research has reported beneficial effects of melatonin in rodent models of Alzheimer's disease (AD). This study evaluated the effect of ramelteon (Rozerem, a melatonin receptor agonist) on spatial learning & memory and neuropathological markers in a transgenic murine model of AD (the B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mouse strain; hereafter 'AD mice'). Three months of daily ramelteon treatment (~3mg/kg/day), starting at 3 months of age, did not produce an improvement in the cognitive performance of AD mice (water maze). In contrast to wild-type control mice, AD mice did not show any evidence of having learned the location of the escape platform. The cortex and hippocampus of AD mice contained significant quantities of beta-amyloid plaques and PARP-positive (poly ADP ribose polymerase) cells, indicating apoptosis. Six months of ramelteon treatment, starting at 3 months of age, did not produce any change in these neuropathological markers. The ability of long term melatonin treatment to improve cognition and attenuate neuropathology in AD mice did not generalize to this dosage of ramelteon.

Alternate JournalArch Ital Biol
PubMed ID22786833