Melatonin plus physical exercise are highly neuroprotective in the 3xTg-AD mouse

Yoelvis García-Mesa, Lydia Giménez-Llort, Luis C. López, Carmen Venegas, Rosa Cristòfol, Germain Escames, Darío Acuña-Castroviejo, Coral Sanfeliu

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69 Citations (Scopus)


Alzheimer's disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. Several healthy lifestyle options and over-the-counter drugs that it has been suggested delay the onset of the disease are in an experimental phase, but it is unclear whether they will have any therapeutic value against AD. We assayed physical exercise and melatonin in 3xTg-AD male mice aged from 6 to 12 months, therefore from moderate to advanced phases of AD pathology. Analysis of behavior and brain tissue at termination showed differential patterns of neuroprotection for the 2 treatments. Both treatments decreased soluble amyloid β oligomers, whereas only melatonin decreased hyperphosphorylated tau. Melatonin was effective against the immunosenescence that 3xTg-AD mice present. Voluntary physical exercise protected against behavioral and psychological symptoms of dementia such as anxiety, a lack of exploration, and emotionality. Both treatments protected against cognitive impairment, brain oxidative stress, and a decrease in mitochondrial DNA (mtDNA). Interestingly, only the combined treatment of physical exercise plus melatonin was effective against the decrease of mitochondrial complexes. Therefore, melatonin plus physical exercise may exert complementary, additive, or even synergistic effects against a range of disturbances present in AD. © 2012 Elsevier Inc.
Original languageEnglish
Pages (from-to)1124.e13-1124.e29
JournalNeurobiology of Aging
Issue number6
Publication statusPublished - 1 Jan 2012


  • 3xTg-AD mice
  • Alzheimer's disease
  • Melatonin
  • Mitochondrial aging
  • Physical exercise

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