Melatonin ameliorates amygdala-dependent emotional memory deficits in Tg2576 mice by up-regulating the CREB/c-Fos pathway

• Published in: Neuroscience letters Vol. 638; pp. 76 - 82
• Main Authors: Peng, Caixia, Hong, Xiaoping, Chen, Weiqun, Zhang, Hongfeng, Tan, Lu, Wang, Xiong, Ding, Yu, He, Jinrong
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 18.01.2017
• Subjects: Alzheimer’s disease; Amygdala - physiopathology; Amyloid beta-Protein Precursor - genetics; Animals; Basolateral amygdala; c-Fos; Conditioning, Classical; Cues; Cyclic AMP Response Element-Binding Protein - metabolism; Emotional memory; Emotions - drug effects; Fear - drug effects; Humans; Melatonin; Melatonin - pharmacology; Melatonin - therapeutic use; Memory - drug effects; Memory Disorders - drug therapy; Memory Disorders - metabolism; Memory Disorders - psychology; Mice, Transgenic; Proto-Oncogene Proteins c-fos - metabolism; Signal Transduction; Up-Regulation; Basolateral amygdala; c-Fos; Emotional memory; Melatonin; Alzheimer’s disease
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.11.066

•Melatonin improved amygdala-dependent emotional memory in Tg2576 mice.•Melatonin increased the expression of c-fos protein levels in basolateral amygdala.•Melatonin increased the expression of pCREB/CREB ratio in basolateral amygdala.•CREB/c-Fos pathway play critical role for the efficacy of melatonin in Tg2576 mice. The effects of melatonin on spatial memory deficits in Alzheimer’s disease (AD) have been thoroughly investigated. Our previous study demonstrated that melatonin rescues hippocampus-dependent spatial memory deficits by arresting hippocampal pathological progression in an animal model of AD, which occurs via the inhibition of GSK3β and an increase in c-Fos. Based on the interaction between the amygdala and hippocampus, it is important to determine whether melatonin also improves amygdala-dependent emotional memory to understand the mechanism of melatonin amelioration of memory deficits in AD. The basolateral amygdala (BLA) is essential for the processing of emotions, including cued fear conditioning and anxiety. In the present study, we intraperitoneally injected Tg2576 mice with melatonin for 4 months and measured amygdala-dependent emotional memory using cued fear conditioning and a step-down passive avoidance test; the expression of c-Fos, Arc, phosphorylated CREB (pCREB) and other related genes were subsequently measured using Real-time polymerase chain reaction (RT-PCR) and Western blot in BLA. Our findings suggest that melatonin ameliorates amygdala-dependent emotional memory in AD via up-regulation of the pCREB/c-Fos pathway.