Physical Exercise Protects Against Alzheimer's Disease in 3xTg-AD Mice

Abstract

Physical exercise is considered to exert a positive neurophysiological effect that helps to maintain normal brain activity in the elderly. Expectations that it could help to fight Alzheimer's disease (AD) were recently raised. This study analyzed the effects of different patterns of physical exercise on the 3xTg-AD mouse. Male and female 3xTg-AD mice at an early pathological stage (4-month-old) have had free access to a running wheel for 1 month, whereas mice at a moderate pathological stage(7-month-old) have had access either during 1 or 6 months. The non-transgenic mouse strain was used as a control. Parallel animal groups were housed in conventional conditions. Cognitive loss and behavioral and psychological symptoms of dementia (BPSD)-like behaviors were present in the 3xTg-AD mice along with alteration in synaptic function and ong-term potentiation impairment in vivo. Brain tissue showed AD-pathology and oxidative-related changes. Disturbances were more severe at the older age tested. Oxidative stress was higher in males but other changes were similar or higher in females. Exercise treatment ameliorated cognitive deterioration and BPSD-like behaviors such as anxiety and the startle response. Synaptic changes were partially protected by exercise. Oxidative stress was reduced. The best neuroprotection was generally obtained after 6 months of exercise in 7-month-old 3xTg-AD mice. Improved sensorimotor function and brain tissue antioxidant defence were induced in both 3xTg-AD and NonTg mice. Therefore, the benefits of aerobic physical exercise on synapse, redox homeostasis, and general brain function demonstrated in the 3xTg-AD mouse further support the value of this healthy life-style against neurodegeneration.

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

“…At advanced AD stages, promising results of higher cognitive performance after running wheel exercise have been reported in the aged Tg2576 mouse (Nichol et al, 2007;Parachikova et al, 2008) but not in the aged APP23 mouse (Wolf et al, 2006). In a previous study with the 3xTg-AD mouse model (Oddo et al, 2003) we demonstrated that chronic running wheel starting at 1 month of age greatly improves behavior and cognition tested at 7 months of age (García-Mesa et al, 2011). Therefore, 6 months of voluntary physical exercise significantly ameliorated nerve cell and brain tissue functionality throughout early and moderate stages of AD pathology.…”

“…Therefore, 6 months of voluntary physical exercise significantly ameliorated nerve cell and brain tissue functionality throughout early and moderate stages of AD pathology. One of the observed benefits was an amelioration of the cerebral oxidative stress of 3xTg-AD mice (Resende et al, 2008;Giménez-Llort et al, 2010;García-Mesa et al, 2011). However, exercise induction of antioxidant defense (Radak et al, 2008) may not be enough to protect highly oxidized brain tissue at advanced AD stages.…”

Mutation of the 3-Phosphoinositide-Dependent Protein Kinase 1 (PDK1) Substrate-Docking Site in the Developing Brain Causes Microcephaly with Abnormal Brain Morphogenesis Independently of Akt, Leading to Impaired Cognition and Disruptive Behaviors

“…Episodes of immobility (flotation) were measured. On days 7 to 10, circadian motor activity was tested for 84 consecutive hours in a home cage equipped with a running wheel (31).…”

La melatonina como un factor promotor de la diferenciación neuronal: implicaciones en el tratamiento de las demencias

“…77,82 Además, en modelos animales de EA, como los ratones 3xTg-AD, también se ha demostrado que la MEL disminuye los niveles de tau hiperfosforilada así como los síntomas conductuales similares a los de la demencia tales como la ansiedad y la pérdida de la conducta exploratoria. 83 De manera análoga se ha descrito que en animales pinealectomizados hay un incremento en los niveles de tau hiperfosforilada asociados con un detrimento de la cognición. 80 …”