P1‐427: TREADMILL EXERCISE PROTECTS HIPPOCAMPUS AND AMYGDALA FROM NEURODEGENERATION IN ALZHEIMER'S DISEASE TRANSGENIC MICE

Post-mortem examination and brain imaging studies indicate that amygdala and hippocampus are the two most vulnerable regions in the brains of Alzheimer's disease (AD) patients. Previously, we have found that chronic running exercise enhanced the amygdala- and hippocampus-dependent learning and memory via up-regulation of the BDNF-TrkB signaling pathways. In this study, we attempted to investigate the effects of chronic exercise on neuronal functions of amygdala and hippocampus in an APP/PS1 transgenic (Tg) mouse model of AD, at a stage much earlier than the beginning of amyloid deposition. Male Tg mice at two months of age were subjected to moderate treadmill exercise training for two months.The amygdala and hippocampus learning and memory functions were tested by Pavlovian fear conditioning. Dendritic morphology of the neurons in the basolateral amygdala (BLA) and hippocampal CA1 and CA3 regions were examined by single neuron injection of fluorescent dye, lucifer yellow. Levels of BDNF/TrkB signaling molecules and Aβ in the hippocampus and amygdala were quantified. At four months of age, sedentary Tg mice already exhibited abnormalities in the amygdala, including impaired learning and memory performance, reduced dendritic arbor and decreased levels of p-TrkB, p-Akt and p-PKC. These changes were not observed in the hippocampus of 4-month-old sedentary Tg mice. Interestingly, the levels of Aβ in the amygdala were higher than that in the hippocampus. Two months of treadmill exercise training not only restored the Tg-associated deficits in the amygdala (i.e. restored the learning and memory and the dendritic arbor), but also increased the hippocampus-associated memory performance and dendritic arbor of the CA1 and CA3 neurons. Furthermore, the levels of p-TrkB, p-Akt, p-PKC and p-ERK were increased and the levels of Aβ were decreased by exercise training in both the amygdala and hippocampus. Chronic exercise training increases the BDNF signaling molecules and protects amygdalar and hippocampal neurons against AD-related toxicity. Our results suggest that chronic exercise training may delay the onset of AD.