Chronic ramelteon treatment in a mouse model of Alzheimer's disease.
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.
VA Boston Healthcare System/Harvard Medical School, Brockton, MA 02301-5596, USA. james_mckenna@hms.harvard.edu
James Timothy
JT
McKenna
Michael A
MA
Christie
Brianne A
BA
Jeffrey
John G
JG
McCoy
Eunho
E
Lee
Nina P
NP
Connolly
Chris P
CP
Ward
Robert E
RE
Strecker
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006801:Humans; D007192:Indenes / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D058225:Plaque, Amyloid / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D013997:Time Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; D007192:Indenes; C508853:PSEN1 protein, human; D053764:Presenilin-1; C495910:ramelteon; D011065:Poly(ADP-ribose) Polymerases