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

Aggregated amyloid beta (Aß) 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 Aß clearance mechanisms following developed AD-like neuropathology induced by intra-hippocampal Aß1-42 injection in male Wistar rats. We found Aß1-42-treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aß1-42 (sAß1-42), 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. Aß1-42-treated animals also exhibited a higher level of sAß1-42 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 sAß1-42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aß1-42-treated animals. Aß1-42-treated animals subjected to treadmill exercise also revealed decreased levels of sAß1-42 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 Aß 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.

Moderate treadmill exercise ameliorates amyloid-ß-induced learning and memory impairment, possibly via increasing AMPK activity and up-regulation of the PGC-1α/FNDC5/BDNF pathway.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with loss of memory and cognitive abilities. Previous evidence suggested that exercise ameliorates learning and memory deficits by increasing brain derived neurotrophic factor (BDNF) and activating downstream pathways in AD animal models. However, upstream pathways related to increase BDNF induced by exercise in AD animal models are not well known. We investigated the effects of moderate treadmill exercise on Aß-induced learning and memory impairment as well as the upstream pathway responsible for increasing hippocampal BDNF in an animal model of AD. Animals were divided into five groups: Intact, Sham, Aß1-42, Sham-exercise (Sham-exe) and Aß1-42-exercise (Aß-exe). Aß was microinjected into the CA1 area of the hippocampus and then animals in the exercise groups were subjected to moderate treadmill exercise (for 4 weeks with 5 sessions per week) 7 days after microinjection. In the present study the Morris water maze (MWM) test was used to assess spatial learning and memory. Hippocampal mRNA levels of BDNF, peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), fibronectin type III domain-containing 5 (FNDC5) as well as protein levels of AMPK-activated protein kinase (AMPK), PGC-1α, BDNF, phosphorylation of AMPK were measured. Our results showed that intra-hippocampal injection of Aß1-42 impaired spatial learning and memory which was accompanied by reduced AMPK activity (p-AMPK/total-AMPK ratio) and suppression of the PGC-1α/FNDC5/BDNF pathway in the hippocampus of rats. In contrast, moderate treadmill exercise ameliorated the Aß1-42-induced spatial learning and memory deficit, which was accompanied by restored AMPK activity and PGC-1α/FNDC5/BDNF levels. Our results suggest that the increased AMPK activity and up-regulation of the PGC-1α/FNDC5/BDNF pathway by exercise are likely involved in mediating the beneficial effects of exercise on Aß-induced learning and memory impairment.

Narita target heart rate equation underestimates the predicted adequate exercise level in sedentary young boys.

PURPOSE: Optimal training intensity and the adequate exercise level for physical fitness is one of the most important interests of coaches and sports physiologists. The aim of this study was to investigate the validity of the Narita et al target heart rate equation for the adequate exercise training level in sedentary young boys. METHODS: Forty two sedentary young boys (19.07±1.16 years) undertook a blood lactate transition threshold maximal treadmill test to volitional exhaustion with continuous respiratory gas measurements according to the Craig method. The anaerobic threshold (AT) of the participants then was calculated using the Narita target heart rate equation. RESULTS: Hopkin's spreadsheet to obtain confidence limit and the chance of the true difference between gas measurements and Narita target heart rate equation revealed that the Narita equation most likely underestimates the measured anaerobic threshold in sedentary young boys (168.76±15 vs. 130.08±14.36) (Difference ±90% confidence limit: 38.1±18). Intraclass correlation coefficient (ICC) showed a poor agreement between the criterion method and Narita equation (ICC= 0.03). CONCLUSION: According to the results, the Narita equation underestimates the measured AT. It seems that the Narita equation is a good predictor of aerobic not AT which can be investigated in the future studies.