NMC——VTA多巴胺能神经元丢失参与阿尔茨海默病的发生

摘要

Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer’s disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing.

1.Tg2576小鼠在3个月大时就出现VTA DAergic神经元的丢失

2.Tg2576小鼠的DAergic神经元死亡和凋亡和胶质细胞炎症相关

3.6个月大的Tg2576小鼠出现NAc shell的DA含量的下降和奖赏功能的缺陷

4.6个月大的Tg2576小鼠出现海马DA含量下降、突触可塑性下降和记忆缺陷

5.亚慢性补充左旋多巴和司来吉兰可以防止6月大Tg2576小鼠CA3-CA1突触可塑性缺陷

6.亚慢性补充左旋多巴和司来吉兰可以防止海马PSD组成和树突棘密度受损

7.亚慢性补充左旋多巴和司来吉兰可以防止记忆和奖赏功能的缺陷

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