Neurodegeneration in Amygdala Precedes Hippocampus in the APPswe/ PS1dE9 Mouse Model of Alzheimer’s Disease

扁桃形结构 海马体 神经科学 神经退行性变 海马结构 阿尔茨海默病 心理学 基底外侧杏仁核 内科学 医学 疾病
作者
Tzu Wei Lin,Yu Fan Liu,Ying-Hsia Shih,Shean-Jen Chen,Tai Yin Huang,Chia Yuan Chang,Chi-Hsiang Lien,Lung Yu,Shun Hua Chen,Yu Min Kuo
出处
期刊:Current Alzheimer Research [Bentham Science Publishers]
卷期号:12 (10): 951-963 被引量:14
标识
DOI:10.2174/1567205012666151027124938
摘要

Both the hippocampus and amygdala are early vulnerable brain regions in the development of Alzheimer’s disease (AD). However, previous studies mainly focused on characterizing the hippocampus in the pathophysiology of AD, leaving the amygdala less explored. Here, we characterized the structures and functions 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. 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. Likewise, 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. BDNF signaling pathways (e.g. AKT and PKC) were reduced in the amygdala, but not in the hippocampus, of young Tg mice. Furthermore, reduction of 5-HT and elevation of Aβ levels also occurred earlier in the amygdala and were more pronounced than those in the hippocampus. Negative correlations between the levels of 5-HT and Aβ were evident in the amygdala, but not in the hippocampus. Taken together, these results suggest that neurodegeneration occurs earlier in the amygdala than in the hippocampus. We suggest that amygdala function should be incorporated into the cognitive screening tool for the diagnosis of mild cognitive impairment due to AD. Keywords: Alzheimer’s disease, amygdala, dendrite, hippocampus, learning and memory, plasticity.
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