Treadmill exercise protects hippocampus and amygdala from neurodegeneration in Alzheimer’s disease transgenic mice

Abstract

Alzheimer’s disease (AD) is an age-related neurodegenerative disease Results from post-mortem examination and brain imaging studies reveal that neurodegeneration has already occurred in both the hippocampus and amygdala of very early stage AD patients Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function Therefore the objective of this study is to investigate the effect of treadmill exercise on the structure and function of neurons in the hippocampus and amygdala of young (2 3 and 4 months of age) APP/PS1 double transgenic (Tg) mice a widely used AD mouse model These ages are younger than the typical onset time of amyloid deposition (6-months-old) Compared to wild-type littermates (Wt ) Tg mice performed worse in amygdala-dominant memory at all three ages while hippocampus-dominant memory remained intact until 4-month-old The dendritic arbors of neurons in the basolateral amygdala were reduced in Tg mice as early as 2-months-old while the dendritic arbors of neurons in the hippocampal CA1 and CA3 regions were relatively intact The levels of BDNF-TrkB signaling molecules (i e p-TrkB p-Akt and p-PKC) were reduced in the amygdala earlier than in the hippocampus of the Tg mice Ten weeks of treadmill training (from 1 5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice Similarly exercise training also increased the levels of p-TrkB p-Akt and p-PKC in the hippocampus and amygdala Furthermore exercise training reduced the levels of soluble Aβ in the hippocampus and amygdala Exercise training did not change the levels of amyloid precursor protein or receptor for advanced glycation end-product but significantly increased the levels of low-density lipoprotein-related protein-1 in both brain regions of the Tg mice Taken together these results suggest that neurodegeneration occurs earlier in the amygdala than in the hippocampus Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration probably via enhancements of BDNF signaling pathways and Aβ clearance Therefore we suggest that running exercise may serve as a means to delay the onset of AD

Date of Award	2015 Mar 18
Original language	English
Supervisor	Yu-Min Kuo (Supervisor)