Beneficial effects of melatonin in a rat model of sporadic Alzheimer's disease

Biogerontology. 2015 Jun;16(3):303-16. doi: 10.1007/s10522-014-9547-7. Epub 2014 Dec 17.


Melatonin synthesis is disordered in patients with Alzheimer's disease (AD). To determine the role of melatonin in the pathogenesis of AD, suitable animal models are needed. The OXYS rats are an experimental model of accelerated senescence that has also been proposed as a spontaneous rat model of AD-like pathology. In the present study, we demonstrate that disturbances in melatonin secretion occur in OXYS rats at 4 months of age. These disturbances occur simultaneously with manifestation of behavioral abnormalities against the background of neurodegeneration and alterations in hormonal status but before the signs of amyloid-β accumulation. We examined whether oral administration of melatonin could normalize the melatonin secretion and have beneficial effects on OXYS rats before progression to AD-like pathology. The results showed that melatonin treatment restored melatonin secretion in the pineal gland of OXYS rats as well as the serum levels of growth hormone and IGF-1, the level of BDNF in the hippocampus and the healthy state of hippocampal neurons. Additionally, melatonin treatment of OXYS rats prevented an increase in anxiety and the decline of locomotor activity, of exploratory activity, and of reference memory. Thus, melatonin may be involved in AD progression, whereas oral administration of melatonin could be a prophylactic strategy to prevent or slow down the progression of some features of AD pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aging, Premature / metabolism*
  • Aging, Premature / physiopathology
  • Aging, Premature / prevention & control*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / prevention & control*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition / drug effects
  • Cognition / physiology
  • Disease Models, Animal*
  • Growth Hormone / blood
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Locomotion / drug effects
  • Locomotion / physiology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Melatonin / administration & dosage
  • Melatonin / metabolism*
  • Melatonin / pharmacology*
  • Pineal Gland / drug effects
  • Pineal Gland / metabolism*
  • Rats
  • Rats, Mutant Strains
  • Rats, Wistar


  • Amyloid beta-Peptides
  • Brain-Derived Neurotrophic Factor
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Melatonin