Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.
Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.
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DOI：
10.1371/journal.pone.0024325
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Castanon N
中科院分区：
文献类型：
--
作者：
Dinel AL;André C;Aubert A;Ferreira G;Layé S;Castanon N
越来越多的临床数据表明外周炎症可能参与代谢综合征(METS)相关神经精神症状的发病机制。然而，问题是，METS中行为改变的增加是否也与中枢性炎症有关，即大脑中特别涉及控制行为的区域的细胞因子激活。为了回答这个问题，我们在蛋氨酸小鼠模型中，即糖尿病和肥胖的db/db小鼠，以及它们健康的db/+胎鼠中，测量了情绪行为和记忆表现，以及血浆水平和大脑(海马体；下丘脑)炎性细胞因子的表达。我们的结果显示，db/db小鼠在旷野和高架正迷宫中表现出更多的焦虑样行为(即在每个设备的焦虑区花费的时间百分比减少)，但不像强迫游泳和尾部悬挂测试中的不动时间所评估的那样表现出抑郁样行为。此外，db/db小鼠表现出空间识别记忆受损(海马体依赖的任务)，但对象识别记忆没有改变(海马体非依赖的任务)。Db/db小鼠的行为改变与海马区在焦虑样行为和空间记忆中的既定作用一致，与炎性细胞因子(白介素1β、肿瘤坏死因子α和白介素6)的增加和脑源性神经营养因子在海马区而不是下丘脑的表达减少有关。这些结果有力地表明，细胞因子和涉及海马体的中枢过程之间的相互作用是db/db小鼠行为改变的重要促成因素。这些发现可能被证明是有价值的，以引入新的方法来治疗与METS相关的神经精神并发症。
Converging clinical data suggest that peripheral inflammation is likely involved in the pathogenesis of the neuropsychiatric symptoms associated with metabolic syndrome (MetS). However, the question arises as to whether the increased prevalence of behavioral alterations in MetS is also associated with central inflammation, i.e. cytokine activation, in brain areas particularly involved in controlling behavior. To answer this question, we measured in a mouse model of MetS, namely the diabetic and obese db/db mice, and in their healthy db/+ littermates emotional behaviors and memory performances, as well as plasma levels and brain expression (hippocampus; hypothalamus) of inflammatory cytokines. Our results shows that db/db mice displayed increased anxiety-like behaviors in the open-field and the elevated plus-maze (i.e. reduced percent of time spent in anxiogenic areas of each device), but not depressive-like behaviors as assessed by immobility time in the forced swim and tail suspension tests. Moreover, db/db mice displayed impaired spatial recognition memory (hippocampus-dependent task), but unaltered object recognition memory (hippocampus-independent task). In agreement with the well-established role of the hippocampus in anxiety-like behavior and spatial memory, behavioral alterations of db/db mice were associated with increased inflammatory cytokines (interleukin-1β, tumor necrosis factor-α and interleukin-6) and reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus but not the hypothalamus. These results strongly point to interactions between cytokines and central processes involving the hippocampus as important contributing factor to the behavioral alterations of db/db mice. These findings may prove valuable for introducing novel approaches to treat neuropsychiatric complications associated with MetS.