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Alzheimer's disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40-Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Ab, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-moold 3-Tg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 wk of exercise combined with 40-Hz light flickering on cognitive function by analyzing neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3-Tg-AD mouse model. Five-month-old 3-Tg-AD mice performed 12 wk of exercise with 40-Hz light flickering administered independently and in combination. Spatial learning and memory, long-term memory, hippocampal Ab, tau, neuroinflammation, proinflammatory cytokine expression, mitochondrial function, and neuroplasticity were analyzed. Ab and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reducing neuroinflammation and proinflammatory cytokines. Furthermore, mitochondrial function improved, apoptosis was reduced, and synapse-related protein expression increased. Overall, exercise with 40-Hz light flickering was significantly more effective than exercise or 40-Hz light flickering alone, and the improvement was comparable to the levels in the nontransgenic aged-match control group. Our results indicate a synergistic effect of exercise and 40-Hz light flickering on pathological improvements in the hippocampus during early AD-associated cognitive impairment. NEW & NOTEWORTHY Exercising in a 40-Hz light flicker environment was more effective than exercise or 40-Hz light flicker alone. This synergistic effect may prevent cognitive dysfunction by inhibiting Ab, tau pathway, and neuroinflammation and enhancing neuroplasticity and mitochondrial functions in the hippocampus during early Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Abstract Background Exercise promotes brain health and improves cognitive functioning in the elderly, while 40-Hz light flickering through the visual cortex reduces amyloid beta (Aβ) by stabilizing gamma oscillation. We examined whether exercise was associated with hippocampus-mediated improvement in cognitive functioning in the 3xTg-Alzheimer’s disease (3xTg-AD) murine model following exposure to 40-Hz light flickering and exercise. Methods We subjected 12-month-old 3xTg-AD mice to exercise and 40-Hz light flickering for 3 months to investigate spatial learning, memory, long-term memory, Aβ levels, tau levels, mitochondrial functioning including Ca2+ retention and H2O2 emission, apoptosis, and neurogenesis in the hippocampus. Results Treatments had a positive effect; however, the combination of exercise and 40-Hz light flickering exposure was most effective in reducing Aβ and tau levels. Reducing Aβ and tau levels by combination of exercise and 40-Hz light flickering improves Ca2+ homeostasis and reactive oxygen species such as H2O2 in mitochondria and apoptosis including bax, bcl-2, cytochrome c, and cleaved caspase-3 and cell death, cell differentiation, and neurogenesis in the 3xTg-AD model of the hippocampus, resulting in improving cognitive impairment such as spatial learning, memory and long term memory. Conclusion Our results show that exercising in a 40-Hz light flickering environment may improve cognitive functioning by reducing Aβ and tau levels, thereby enhancing mitochondrial function and neuroplasticity.

Background: Exercise promotes brain health and improves cognitive functioning in the elderly, while 40-Hz light flickering through the visual cortex reduces amyloid beta (Aβ) by stabilizing gamma oscillation. We examined whether exercise was associated with hippocampus-mediated improvement in cognitive functioning in the 3xTg-Alzheimer's disease (3xTg-AD) murine model following exposure to 40-Hz light flickering and exercise. Methods: We subjected 12-month-old 3xTg-AD mice to exercise and 40-Hz light flickering for 3 months to investigate spatial learning, memory, long-term memory, Aβ levels, tau levels, mitochondrial functioning including Ca2+ retention and H2O2 emission, apoptosis, and neurogenesis in the hippocampus. Results: Treatments had a positive effect; however, the combination of exercise and 40-Hz light flickering exposure was most effective in reducing Aβ and tau levels. Reducing Aβ and tau levels by combination of exercise and 40-Hz light flickering improves Ca2+ homeostasis and reactive oxygen species such as H2O2 in mitochondria and apoptosis including bax, bcl-2, cytochrome c, and cleaved caspase-3 and cell death, cell differentiation, and neurogenesis in the 3xTg-AD model of the hippocampus, resulting in improving cognitive impairment such as spatial learning, memory and long term memory. Conclusion: Our results show that exercising in a 40-Hz light flickering environment may improve cognitive functioning by reducing Aβ and tau levels, thereby enhancing mitochondrial function and neuroplasticity. [ABSTRACT FROM AUTHOR]