Abstract
Alzheimer’s disease (AD) is characterized by deficits in learning and memory. A pathological feature of AD is the alterations in the number and size of synapses, axon length, dendritic complexity, and dendritic spine numbers in the hippocampus and prefrontal cortex. Treadmill exercise can enhance synaptic plasticity in mouse or rat models of stroke, ischemia, and dementia. The aim of this study was to examine the effects of treadmill exercise on learning and memory, and structural synaptic plasticity in 3×Tg-AD mice, a mouse model of AD. Here, we show that 12 weeks treadmill exercise beginning in three-month-old mice improves spatial working memory in six-month-old 3×Tg-AD mice, while non-exercise six-month-old 3×Tg-AD mice exhibited impaired spatial working memory. To investigate potential mechanisms for the treadmill exercise-induced improvement of spatial learning and memory, we examined structural synaptic plasticity in the hippocampus and prefrontal cortex of six-month-old 3×Tg-AD mice that had undergone 12 weeks of treadmill exercise. We found that treadmill exercise led to increases in synapse numbers, synaptic structural parameters, the expression of synaptophysin (Syn, a presynaptic marker), the axon length, dendritic complexity, and the number of dendritic spines in 3×Tg-AD mice and restored these parameters to similar levels of non-Tg control mice without treadmill exercise. In addition, treadmill exercise also improved these parameters in non-Tg control mice. Strengthening structural synaptic plasticity may represent a potential mechanism by which treadmill exercise prevents decline in spatial learning and memory and synapse loss in 3×Tg-AD mice.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disease most often characterized by memory impairment and cognitive decline [1]
We found that 12 weeks of treadmill exercise prevented a decline in spatial learning and memory in six-month-old 3×Tg-AD mice and that treadmill exercise led to enhanced structural synaptic plasticity by increasing synapse numbers and synaptic structural parameters, the expression of synaptophysin (Syn), the axon length, dendritic complexity, and the dendritic spine numbers
High magnification view of synapses in the prefrontal cortex is shown in the red square box in the bottom. (B,C) The synapse numbers of hippocampus (B) and prefrontal cortex (C) were significantly decreased in the 3×Tg-AD control group compared to the non-Tg control group (*** p < 0.001, n = 6 image sections), and this decrease was blocked by treadmill exercise pretreatment both in the hippocampus (B) and prefrontal cortex (C) (*** p < 0.001, n = 6 image sections)
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disease most often characterized by memory impairment and cognitive decline [1]. Previous studies suggest that Aβ and tau can impair memory by disrupting synaptic plasticity in the hippocampus and prefrontal cortex [7,8]. This synaptic plasticity includes activitydependent changes in the synaptic efficacy and remodeling, axonal sprouting and dendritic remodeling, and dendritic spine dynamics. Soluble Aβ-oligomers at nanomolar concentrations, extracted directly from the cerebral cortex of typical AD patients or generated from synthetic peptide, disrupted the memory of a learned behavior by potently inhibiting long term potentiation (LTP), enhancing long term depression (LTD), reducing dendritic spine density of hippocampus [9–11]. AD is increasingly prevalent around the world, and yet no available treatments can cure or slow the progression of this disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
