Cognitive impairment is a central feature of neurodegenerative and vascular disorders and is linked to disrupted synaptic plasticity. Vascular endothelial growth factor (VEGF) has a role in both cerebrovascular regulation and synaptic maintenance, suggesting it may link vascular dysfunction to cognitive decline. This study in Behavioral Brain Research examines whether aerobic exercise improves cognition in apolipoprotein E–deficient (ApoE−/−) mice through VEGF-mediated mechanisms. Compared with sedentary ApoE−/− controls, exercised ApoE−/− mice showed improved learning and memory, reduced brain tissue damage and decreased amyloid-β deposition. Exercise increased dendritic spine density and synapse-associated protein expression in the cortex and hippocampus. These synaptic benefits were associated with activation of the VEGF/ERK (extracellular signal-regulated kinases) signaling pathway. In parallel, aerobic exercise improved vascular pathology, reduced aortic lipid accumulation and preserved cerebral vascular density. Together, these findings show that aerobic exercise mitigates cognitive dysfunction in ApoE-deficient mice by enhancing synaptic plasticity and vascular health, stressing VEGF/ERK signaling as a promising therapeutic target.
Original reference: Wang, Z. et al. Behav. Brain Res. 502, 116005 (2026)
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