Treadmill Exercise Ameliorates Spatial Learning and Memory Deficits Through Improving the Clearance of Peripheral and Central Amyloid-Beta Levels

Abstract

Aggregated amyloid beta (Aβ) peptides are believed to play a decisive role in the pathology of Alzheimer's disease (AD). Previous evidence suggested that exercise contributes to the improvement of cognitive decline and slows down pathogenesis of AD; however, the exact mechanisms for this have not been fully understood. Here, we evaluated the effect of a 4-week moderate treadmill exercise on spatial memory via central and peripheral Aβ clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aβ injection in male Wistar rats. We found Aβ-treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aβ (sAβ), decreased mRNA and protein expression of neprilysin (NEP), insulin degrading enzyme (IDE) and low-density lipoprotein receptor-related protein-1 (LRP-1) in the hippocampus. Aβ-treated animals also exhibited a higher level of sAβ and a lower level of soluble LRP-1 (sLRP-1) in plasma, as well as a decreased level of LRP-1 mRNA and protein content in the liver. However, exercise training improved the spatial learning and memory deficits, reduced both plaque load and sAβ levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aβ-treated animals. Aβ-treated animals subjected to treadmill exercise also revealed decreased levels of sAβ and increased levels of sLRP-1 in plasma, as well as increased levels of LRP-1 mRNA and protein in the liver. In conclusion, our findings suggest that exercise-induced improvement in both of central and peripheral Aβ clearance are likely involved in ameliorating spatial learning and memory deficits in an animal model of AD. Future studies need to determine their relative contribution.

Experimental Investigation of the Effects of Acute Exercise on Real-World Ecological Memory

“…This finding, however, does not align with meta-analytic research showing that exercise may have greater effects on memory function (not specifically face-name memory) for younger adults (vs. older adults) [39]. Lastly, although we observed null effects of acute exercise on face-name memory performance, which is a paired associative task, with such tasks involving hippocampal integration [50], animal work generally demonstrates that acute exercise can have profound effects on hippocampal neuronal activity [1] and hippocampal-dependent memory function [19,46].…”

Meta-analysis: Resistance Training Improves Cognition in Mild Cognitive Impairment

“…On the one hand, exercise reduces the production of toxic amyloid-β peptides by inhibiting β-and γ-secretases that promote the liberation of amyloid-β from the amyloid precursor protein [19]. On the other hand, exercise can increase amyloid-β degrading enzymes [17], which may reduce the accumulation of amyloid plaques. In addition, exercise can promote the exchange of water and soluble contents between the cerebrospinal fluid and the interstitial fluid, which plays an important role in the clearance of amyloid plaques [18].…”

“…Studies show that exercise may promote neuroplasticity and play a neuroprotective role by affecting insulin-like growth factor-1, anti-inflammation and brain-derived neurotrophic factor pathways [11][12][13][14][15]. Additionally, exercise, especially resistance training, may affect the burden of amyloid plaques, which are associated with cognitive decline [16][17][18][19]. One study found that resistance training can directly decrease circulating insulin [20], of which an increase may affect the distribution of amyloid 40 and 42 in brain regions, resulting in the accumulation of amyloid plaques [21,22].…”

Strength exercise suppresses STZ‐induced spatial memory impairment and modulates BDNF/ERK‐CAMKII/CREB signalling pathway in the hippocampus of mice

“…Research shows that healthy lifestyle improves mental activity and reduces the risk of various diseases . Indeed, it has been reported that nonpharmacological interventions improve neural repair and synaptic plasticity in the central nervous system (CNS) .…”