The interaction between acute oligomer Abeta(1-40) and stress severely impaired spatial learning and memory.
In this study, we investigated whether stress can enhance the toxicity of oligomer Abeta(1-40) in the mouse brain. Stress was applied to the animals, consisting of a 2-day inescapable foot shock followed by 3-weekly situation reminders (SRs). We found that stress significantly affected not only the amygdala-dependent (anxiety) but also the hippocampal-dependent (spatial learning and memory) behaviors through the oxidative damage caused in these two regions. However, oligomer Abeta(1-40) treatment alone did not induce behavioral impairment. In addition, combined oligomer Abeta(1-40) and stress treatment increased the glucocorticoid receptor (GR)/mineralocorticoid receptor (MR) ratio and the expression of corticotrophin releasing factor 1 (CRF-1) receptor in the hippocampus. Changes in the components of the hypothalamic-pituitary-adrenal (HPA) axis, such as the GR/MR ratio and CRF-1 level, were observed, accompanied by increasing Abeta accumulation, oxidative stress, nuclear transcription factor (NF-kappaB) hypoactivity, and apoptotic signaling in the hippocampus, and decreasing calbindin D28K and NMDA receptor 2A/2B (NR2A/2B) in the hippocampus, along with alteration of the cholinergic neurons (ChAT) in the medium septum/diagnoid band (MS/DB), noradrenergic neurons (TH) in the locus coeruleus (LC), and serotonergic neurons (5-HT) in the Raphe nucleus. Therefore, apoptosis and synaptic dysfunction in the hippocampus severely induced the impairment of spatial learning and memory. These results suggest that stress may play an important role in the early stages of Alzheimer's disease (AD), and an antioxidant strategy might be a potential therapeutic approach for stress-mediated disorders.
Huang
Hei-Jen
HJ
Department of Life Science, National Taiwan Normal University, Taipei 116, Taiwan.
Liang
Keng-Chen
KC
Chang
Yen-Yu
YY
Ke
Hsing-Chieh
HC
Lin
Jia-Yu
JY
Hsieh-Li
Hsiu Mei
HM
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004597:Electroshock; D006624:Hippocampus / Q000503:physiopathology; D007858:Learning / Q000502:physiology; D007859:Learning Disabilities / Q000503:physiopathology*; D008125:Locus Coeruleus / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism*; D011897:Random Allocation; D011903:Raphe Nuclei / Q000503:physiopathology; D013028:Space Perception / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)