Melatonin Attenuates Memory Impairment, Amyloid-β Accumulation, and Neurodegeneration in a Rat Model of Sporadic Alzheimer's Disease

J Alzheimers Dis. 2015;47(1):103-16. doi: 10.3233/JAD-150161.


Melatonin is a multifunctional molecule and plays a crucial role in the regulation of circadian rhythms. The role of melatonin in the protection of the central nervous system is well documented. Therefore, melatonin was proposed as a possible therapeutic agent for reducing the severity of Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by cognitive decline and memory dysfunction. Recently, we showed beneficial neuroprotective effects of prophylactic supplementation with melatonin in a suitable model of sporadic AD: OXYS rats, which exhibit disturbances in melatonin secretion. In the present study, we demonstrated that melatonin administration, when started at the age of active progression of AD-like pathology, decreased the amyloid-β1 - 42 and amyloid-β1 - 40 levels in the hippocampus and amyloid-β1 - 42 levels in the frontal cortex of OXYS rats. Furthermore, oral administration of melatonin slowed down degenerative alterations in hippocampal neurons of OXYS rats. The most noticeable improvement was observed in the CA1 region of the hippocampus. Melatonin administration prevented the decrease in the mitochondria-occupied portion of the neuronal volume and improved the ultrastructure of mitochondria in the neurons of the CA1 region. Additionally, melatonin treatment of OXYS rats slowed down an increase in anxiety and deterioration of reference memory. Thus, melatonin administration could alleviate the burden of AD and may be considered a promising pharmaceutical treatment of the disease.

Keywords: Alzheimer’s disease; melatonin; neurodegeneration; senescence-accelerated OXYS rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Antioxidants / therapeutic use*
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Maze Learning / drug effects
  • Melatonin / therapeutic use*
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Memory Disorders / genetics
  • Mutation / genetics
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / genetics
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / ultrastructure
  • Presenilin-1 / genetics
  • Presenilin-2 / genetics
  • Rats
  • Rats, Transgenic
  • Rats, Wistar


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Antioxidants
  • Presenilin-1
  • Presenilin-2
  • Melatonin