da Costa Neto Ivaniro Rodrigues, do Amaral Junior Fabio Leite, da Silva Arruda Bernardo Freire, Castro Micaele Maria Lopes, Carvalho Chaves de Siqueira Mendes Fabíola de, Anthony Daniel Clive, de Oliveira Brites Dora Maria Tuna, Diniz Cristovam Wanderley Picanço, Sosthenes Marcia Consentino Kronka
Laboratório de Investigações em Neurodegeneração e Infecção, Instituto de Ciências Biológicas, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA 66073-005, Brazil; Universidade da Amazônia, Ananindeua, PA 67113-901, Brazil.
Laboratório de Investigações em Neurodegeneração e Infecção, Instituto de Ciências Biológicas, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA 66073-005, Brazil.
Ann Anat. 2025 Feb;258:152356. doi: 10.1016/j.aanat.2024.152356. Epub 2024 Nov 27.
The dentate gyrus plays a crucial role in learning and spatial memory, particularly in its middle third molecular layer, which receives the primary afferent input via the medial perforant path. Interestingly, changes in masticatory activity are described to affect this region with visible astrogliosis, release of pro-inflammatory cytokines and oxidative stress, affecting synaptic physiology, and cognition. This study aimed to investigate the impact of altered masticatory activity on spatial memory in young Swiss albino mice, correlating these effects with morphological changes in astrocytes. The mice were divided into three groups: Hard diet with pellets (HD), hard diet/soft diet (HD/SD, reduced masticatory activity), and HD/SD/HD (rehabilitated). The Morris water maze test was used to measure escape latency, while three-dimensional microscopic reconstruction methods provided morphometric data on the astrocytes. Hierarchical clustering analysis validated the existence of four morphological subtypes with decreasing complexity (AST1, AST2, AST3, and AST4), in the outer, middle, and inner thirds of the dentate gyrus molecular layer. Changes in masticatory activity affected the number and distribution of astrocytes subtypes excepting AST3 in the middle third layer. Canonical discriminant function analysis indicated that complexity was the variable most influencing cluster formation. Correlation tests between complexity and escape latency for each animal group showed a significant correlation with a large effect size of 60 % [Pearson's R: 0.605, p < 0.001] in the HD group in the middle third, which was disrupted by altered masticatory activity. AST3 morphotype in the middle third showed a linear correlation with learning and spatial memory functions in the HD group [Pearson's R: 0.624, p < 0.001] that disappeared with a reduction in masticatory activity, and nor restored by diet rehabilitation. This finding was not observed for inner and outer layers, supporting the contribution of middle third AST3 to learning and spatial memory. Group comparison tests also revealed that diet differentially impacts astrocyte subpopulations on each third of the dentate gyrus molecular layer. Data validate the influence of the masticatory activity on astrocyte complexity and suggest the existence of AST3 association with spatial memory and learning tasks in young female mice. Further research on the underlying mechanisms of these relationships is essential to identify potential therapeutic targets for cognitive disorders and to develop effective interventions to preserve cognitive function.
齿状回在学习和空间记忆中起着关键作用，尤其是在其中间三分之一的分子层，该层通过内侧穿通路径接收主要传入输入。有趣的是，咀嚼活动的变化被描述为会影响该区域，导致明显的星形胶质细胞增生、促炎细胞因子释放和氧化应激，进而影响突触生理学和认知。本研究旨在调查改变咀嚼活动对年轻瑞士白化小鼠空间记忆的影响，并将这些影响与星形胶质细胞的形态变化相关联。将小鼠分为三组：硬颗粒饲料组（HD）、硬饲料/软饲料组（HD/SD，咀嚼活动减少）和HD/SD/HD组（恢复组）。使用莫里斯水迷宫试验测量逃避潜伏期，同时三维显微镜重建方法提供星形胶质细胞的形态计量数据。层次聚类分析验证了在齿状回分子层的外、中、内三分之一处存在四种形态亚型，其复杂性逐渐降低（AST1、AST2、AST3和AST4）。咀嚼活动的变化影响了中间三分之一层中除AST3之外的星形胶质细胞亚型的数量和分布。典型判别函数分析表明，复杂性是最影响聚类形成的变量。对每个动物组的复杂性和逃避潜伏期进行的相关性测试显示，在中间三分之一的HD组中存在显著相关性，效应大小为60%[皮尔逊相关系数：0.605，p<0.001]，咀嚼活动的改变会破坏这种相关性。中间三分之一的AST3形态型与HD组的学习和空间记忆功能呈线性相关[皮尔逊相关系数：0.624，p<0.001]，随着咀嚼活动的减少这种相关性消失，并且饮食恢复后也未恢复。在内层和外层未观察到这一发现，这支持了中间三分之一的AST3对学习和空间记忆的贡献。组间比较测试还表明，饮食对齿状回分子层每三分之一处的星形胶质细胞亚群有不同影响。数据验证了咀嚼活动对星形胶质细胞复杂性的影响，并表明在年轻雌性小鼠中存在AST3与空间记忆和学习任务的关联。对这些关系的潜在机制进行进一步研究对于确定认知障碍的潜在治疗靶点以及开发有效的干预措施以保护认知功能至关重要。
