Regular Exercise Enhances Cognitive Function and Intracephalic GLUT Expression in Alzheimer’s Disease Model Mice

Abstract

Brain energy metabolic impairment is one of the main features of Alzheimer's disease (AD) and is considered an underlying factor involved in cognitive impairment. Therefore, brain energy metabolism may represent a new therapeutic target for AD medical interventions. Among nutrients providing energy, glucose, the primary energy source, cannot cross the blood-brain barrier freely without specific glucose transporters (GLUTs), which are essential for the maintenance of cerebral energy metabolism homeostasis. Several converging lines of evidence suggest that GLUT1 deficiency in mice leads to synapse reduction and dysregulation coupled with mitochondrial morphological changes. In this study, the results revealed that regular exercise (RE) decreased the expression of amyloid-␤ and phosphorylated tau by western blot, and enhanced the spatial learning and exploration ability of AD model mice as assessed by Morris water maze test. Mitochondrial cristae and edges were clear and intact, ATP production in the brain raised, the number of synapses increased, and GLUT1 and GLUT3 expression levels improved in the central nervous system (CNS) in AD model mice after RE. Changes in GLUT1 and GLUT3 expression at the protein level after RE are an important part of energy metabolic adaptation in AD model mice. Learning and memory improvement are highly associated with mitochondrial integrity and sufficient synapses in the CNS. This research suggests that increased brain energy metabolism attributed to RE exhibits promising therapeutic potential for AD.

Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease

“…For instance, 6-month-old APP/PS1 mice subjected to regular exercise during 4 weeks exhibited improved learning and spatial memory together with decreased levels of Aβ and p-Tau in the cortex and hippocampus. Additionally, it promoted enhanced mitochondrial function and increased synaptic density (Pang et al, 2019). Likewise, it was recently reported that hippocampus-dependent memory and synaptic puncta were positively modulated in 12-month-old mice of the same strain subjected to running during 4 months (Zhang et al, 2020).…”

Brain Glucose Transporters: Role in Pathogenesis and Potential Targets for the Treatment of Alzheimer’s Disease

“…An animal study has revealed that regular exercise decreases the expression of Aβ and phosphorylated tau production, with increased production of ATP in the brain. Researchers have found an increased number of synapses and improved expression levels of Glut1 and Glut3 expression in the central nervous system in a mouse model of AD [ 163 ].…”

Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health

“…In mice, acute aerobic exercise (voluntary wheel running) led to an increase in expression of GLUT1 in the brain (Allen & Messier, 2013). Similarly, regular exercise in mice increased expression of GLUT1 in cardiomyocytes (Jiang et al, 2020) and the central nervous system (Pang et al, 2019). In addition, upregulation of GLUT1 in the cortex was reported after a single bout of aerobic exercise in rats (Takimoto & Hamada, 2014).…”