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

Abstract

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 two 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 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.

Melatonin for Sleep Disorders in Patients with Neurodegenerative Diseases

“…In vitro, beta-amyloid toxicity and aggregation are decreased by melatonin [48][49][50][51]. In animal AD models, melatonin reduces the neurotoxicity and deposition of beta-amyloid, decreases oxidative stress, increases survival time, and protects against cognitive decline [52][53][54][55][56][57][58]. Melatonin decreases proinflammatory cytokines in rats injected with beta-amyloid [59].…”

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

“…Conversely, exercise is a robust positive modulator of hippocampal neurogenesis and also has cognitive enhancement effects in both animal models and human subjects (Yau et al, 2014). In animal models of AD, exercise has been shown to reduce AD pathology by reducing A␤ burden and tau hyperphosphorylation, and also to alleviate cognitive decline (Garcia-Mesa et al, 2012;Liu et al, 2013;Tapia-Rojas et al, 2016). However, to date, there has been little focus on exercise-induced effects on hippocampal neurogenesis and inflammation in AD models.…”

Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP+ toxicity

“…On the other hand, reports demonstrate that long-term moderate exercise induces low level of reactive oxygen species (ROS), which may activate the endogenous antioxidant defense system (Elokda et al, 2010;Somani et al, 1995), though highintensity acute exercise increases oxidative stress and vulnerability to brain injury (Aguiar et al, 2010;Teixeira et al, 2009). The induction of adaptive antioxidant defense by regular exercise has therefore been suggested to be able to prevent oxidative stress-associated aging (Navarro et al, 2004) and neurodegeneration (Cechetti et al, 2012;Garcia-Mesa et al, 2012). Parkinson's disease (PD) is a progressive form of nigrostriatal dopaminergic neurodegeneration accompanied by movement disorders.…”