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

Arch Ital Biol. 2012 Mar;150(1):5-14. doi: 10.4449/aib.v149i5.1375.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / complications
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Apoptosis / genetics
  • Brain / drug effects
  • Brain / metabolism*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / etiology
  • Disease Models, Animal
  • Follow-Up Studies
  • Humans
  • Indenes / therapeutic use*
  • Maze Learning / drug effects
  • Mice
  • Mice, Transgenic
  • Mutation / genetics
  • Plaque, Amyloid / pathology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Presenilin-1 / genetics
  • Time Factors


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Antipsychotic Agents
  • Indenes
  • PSEN1 protein, human
  • Presenilin-1
  • ramelteon
  • Poly(ADP-ribose) Polymerases