Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance.
Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance.
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DOI：
10.1016/j.bbadis.2015.08.016
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Inestrosa NC
中科院分区：
文献类型：
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作者：
Cisternas P;Salazar P;Serrano FG;Montecinos-Oliva C;Arredondo SB;Varela-Nallar L;Barja S;Vio CP;Gomez-Pinilla F;Inestrosa NC
代谢综合征（MetS）是一种全球性流行病，其涉及包括糖尿病和肥胖症的代谢紊乱谱。MetS对大脑的影响正成为一个关注的问题，然而，对所涉及的机制的理解不足限制了治疗策略的发展。我们通过将小鼠暴露于果糖喂养7周来诱导MetS样条件。海马体以长时程增强（LTP）和长时程抑制（LTD）形式维持突触可塑性的能力急剧恶化。暴露于果糖的小鼠表现出海马体中接触区数量和突触后密度（PSD）大小的减少，以及海马体神经发生的减少。脂质过氧化作用增加，可能与质膜兴奋性不足有关。与整体海马功能障碍一致，海马依赖性学习和记忆表现随后下降，即，空间学习和情景记忆。大部分代谢综合征在脑内的病理后果在停止果糖喂养3个月后被逆转。这些结果是新颖的，表明MetS触发了一系列分子事件，这些事件破坏了海马的功能可塑性，以及学习和记忆功能的特定方面。总体信息引起了人们对过量摄入果糖对神经系统疾病病理学造成的风险的担忧。
Metabolic syndrome (MetS) is a global epidemic, which involves a spectrum of metabolic disorders comprising diabetes and obesity. The impact of MetS on the brain is becoming to be a concern, however, the poor understanding of mechanisms involved has limited the development of therapeutic strategies. We induced a MetS-like condition by exposing mice to fructose feeding for 7 weeks. There was a dramatic deterioration in the capacity of the hippocampus to sustain synaptic plasticity in the forms of long-term potentiation (LTP) and long-term depression (LTD). Mice exposed to fructose showed a reduction in the number of contact zones and the size of postsynaptic densities (PSDs) in the hippocampus, as well as a decrease in hippocampal neurogenesis. There was an increase in lipid peroxidation likely associated with a deficiency in plasma membrane excitability. Consistent with an overall hippocampal dysfunction, there was a subsequent decrease in hippocampal dependent learning and memory performance, i.e., spatial learning and episodic memory. Most of the pathological sequel of MetS in the brain was reversed three month after discontinue fructose feeding. These results are novel to show that MetS triggers a cascade of molecular events, which disrupt hippocampal functional plasticity, and specific aspects of learning and memory function. The overall information raises concerns about the risk imposed by excessive fructose consumption on the pathology of neurological disorders.