Fornix volumetric increase and microglia morphology contribute to spatial and recognition-like memory decline in ageing male mice
Fornix volumetric increase and microglia morphology contribute to spatial and recognition-like memory decline in ageing male mice
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DOI：
10.1016/j.neuroimage.2022.119039
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发表时间：
2022-03-06
期刊：
影响因子：
5.7
通讯作者：
Resendez-Perez, Diana
中科院分区：
文献类型：
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作者：
Cardenas-Tueme, Marcela;Angel Trujillo-Villarreal, Luis;Resendez-Perez, Diana
衰老在血液和大脑中显示出低级别的促炎症特征。促炎细胞因子的积累、小胶质细胞活化和脑中体积变化与衰老模型中的认知能力下降相关。然而，它们之间的相互作用并不完全清楚。在这里，我们的目的是在全球范围内确定一个年龄依赖性的促炎性特征和小胶质细胞形态可塑性，有利于与认知能力下降相关的大脑中的主要体积变化。对2个月、12个月和20个月大的雄性C57 BL/6小鼠获得的行为数据进行聚类分析，发现Y型迷宫、巴恩斯迷宫、物体识别（NORT）和物体定位测试（奥尔特）后存在年龄依赖性的认知下降。通过基于变形的脑形态测量学（DBM）进行的全球磁共振成像（MRI）分析发现，在衰老过程中，穹窿体积增加，左内侧内嗅皮层（MEntC）减少。值得注意的是，穹窿显示促炎细胞因子的积累增加，而左侧MEntC显示减少。小胶质细胞的形态学评估也证实了穹窿中的活跃和营养不良表型以及左侧MEntC中的监视表型。最后，生物学模型显示，年龄相关的穹窿体积增加与营养不良性小胶质细胞和认知障碍有关，这一点可以通过检查物体位置和新奇记忆的任务失败来证明。我们的研究结果表明，小胶质细胞的形态可塑性可能有助于在生理老化过程中与认知能力下降相关的脑区域的体积变化。
Ageing displays a low-grade pro-inflammatory profile in blood and the brain. Accumulation of pro-inflammatory cytokines, microglia activation and volumetric changes in the brain correlate with cognitive decline in ageing models. However, the interplay between them is not totally understood. Here, we aimed to globally identify an age-dependent pro-inflammatory profile and microglia morphological plasticity that favors major volume changes in the brain associated with cognitive decline. Cluster analysis of behavioral data obtained from 2-,12and 20-month-old male C57BL/6 mice revealed age-dependent cognitive decline after the Y-maze, Barnes maze, object recognition (NORT) and object location tests (OLT). Global magnetic resonance imageing (MRI) analysis by deformation-based morphometry (DBM) in the brain identified a volume increase in the fornix and a decrease in the left medial entorhinal cortex (MEntC) during ageing. Notably, the fornix shows an increase in the accumulation of pro-inflammatory cytokines, whereas the left MEntC displays a decrease. Morphological assessment of microglia also confirms an active and dystrophic phenotype in the fornix and a surveillance phenotype in the left MEntC. Finally, biological modeling revealed that age-related volume increase in the fornix was associated with dystrophic microglia and cognitive impairment, as evidenced by failure on tasks examining memory of object location and novelty. Our results propose that the morphological plasticity of microglia might contribute to volumetric changes in brain regions associated with cognitive decline during physiological ageing.