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Neurochemical Research

, Volume 43, Issue 8, pp 1561–1574 | Cite as

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

  • Davar Khodadadi
  • Reza GharakhanlouEmail author
  • Naser Naghdi
  • Mona Salimi
  • Mohammad Azimi
  • Atabak Shahed
  • Soomaayeh Heysieattalab
Original Paper

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 Aβ1–42 injection in male Wistar rats. We found Aβ1–42-treated animals showed spatial learning and memory impairment which was accompanied by increased levels of amyloid plaque load and soluble Aβ1–42 (sAβ1–42), 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. Aβ1–42-treated animals also exhibited a higher level of sAβ1–42 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 sAβ1–42 levels, and up-regulated expression of NEP, IDE, and LRP-1 in the hippocampus of Aβ1–42-treated animals. Aβ1–42-treated animals subjected to treadmill exercise also revealed decreased levels of sAβ1–42 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 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.

Keywords

Alzheimer’s disease Spatial learning and memory Treadmill exercise Aβ NEP IDE LRP-1 

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Authors and Affiliations

  • Davar Khodadadi
    • 1
  • Reza Gharakhanlou
    • 1
    Email author
  • Naser Naghdi
    • 2
  • Mona Salimi
    • 2
  • Mohammad Azimi
    • 1
  • Atabak Shahed
    • 3
  • Soomaayeh Heysieattalab
    • 4
  1. 1.Department of Physical Education and Sport Sciences, Faculty of HumanitiesTarbiat Modares UniversityTehranIran
  2. 2.Department of Physiology and PharmacologyPasteur Institute of IranTehranIran
  3. 3.School of Physical Education and Sport SciencesUniversity of TehranTehranIran
  4. 4.Cognitive Neuroscience Division, Faculty of Education and PsychologyUniversity of TabrizTabrizIran

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