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<p>Astrocytes undergo phenotypic changes with aging, contributing to neurodegenerative diseases and cognitive impairments in later life. The temporoammonic (TA) pathway terminates at the <i>stratum lacunosum-moleculare</i> (SLM) of the CA1 region, where astrocytic support is crucial for synaptic plasticity and information processing related to spatial learning and memory. This study tested the hypothesis that age-related morphological changes in astrocytes of the SLM affect cognitive performance and we explored whether masticatory activity modulates these changes. Young (6 months) and aged (18 months) female <i>Swiss albino</i> mice were subjected to three distinct masticatory regimens: a hard diet (HD), HD followed by a soft diet (HD/SD), or HD followed by SD and a return to HD (HD/SD/HD). Cognitive performance was assessed using the Morris Water Maze (MWM), with learning rates calculated from escape latencies throughout five days of trials. After behavioral testing, the mice were culled and immunohistochemical analysis of glial fibrillary acidic protein (GFAP) expression was performed. 3D reconstructions of astrocytes within the SLM were generated and analyzed. Hierarchical clustering identified distinct astrocyte morphotypes, revealing a significant age-related shift from high-complexity astrocytes (AST1) toward lower-complexity subtypes (AST2 and AST3). In the AST1 phenotype, aging did not significantly alter astrocytic complexity in animals maintained under normal masticatory conditions (HD group) in the dorsal region, then, AST1 may represent a more stable and aging-driven astrocytic phenotype, with limited sensitivity to masticatory modulation during advanced aging. Therefore, in AST2 of HD group, aged animals exhibited greater complexity compared to young animals, suggesting the occurrence of adaptive or compensatory astroglial remodeling during physiological aging. Behavioral analysis showed an age-dependent reduction in learning performance in the HD group, where 18&#xa0;M mice exhibited a significantly lower contrast index than 6&#xa0;M old mice on day 4 of the Morris Water Maze task. These findings highlight that morphological changes in astrocytes within the dorsal SLM may contribute to age-related alterations in hippocampus-dependent learning. Overall, maintaining proper mastication may be an effective approach to maintain astrocytic integrity during aging and preserve hippocampus-dependent cognitive function, particularly in older individuals.</p>

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The role of astrocytes in the temporoammonic pathway: masticatory behavior as a neuroprotective strategy against age-related cognitive decline

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Micaele Maria Lopes Castro,
  • Fabio Leite do Amaral,
  • Fabíola de Carvalho Chaves de Siqueira Mendes,
  • Daniel Clive Anthony,
  • Dora Maria Tuna de Oliveira Brites,
  • Cristovam Wanderley Picanço Diniz,
  • Marcia Consentino Kronka Sosthenes

摘要

Astrocytes undergo phenotypic changes with aging, contributing to neurodegenerative diseases and cognitive impairments in later life. The temporoammonic (TA) pathway terminates at the stratum lacunosum-moleculare (SLM) of the CA1 region, where astrocytic support is crucial for synaptic plasticity and information processing related to spatial learning and memory. This study tested the hypothesis that age-related morphological changes in astrocytes of the SLM affect cognitive performance and we explored whether masticatory activity modulates these changes. Young (6 months) and aged (18 months) female Swiss albino mice were subjected to three distinct masticatory regimens: a hard diet (HD), HD followed by a soft diet (HD/SD), or HD followed by SD and a return to HD (HD/SD/HD). Cognitive performance was assessed using the Morris Water Maze (MWM), with learning rates calculated from escape latencies throughout five days of trials. After behavioral testing, the mice were culled and immunohistochemical analysis of glial fibrillary acidic protein (GFAP) expression was performed. 3D reconstructions of astrocytes within the SLM were generated and analyzed. Hierarchical clustering identified distinct astrocyte morphotypes, revealing a significant age-related shift from high-complexity astrocytes (AST1) toward lower-complexity subtypes (AST2 and AST3). In the AST1 phenotype, aging did not significantly alter astrocytic complexity in animals maintained under normal masticatory conditions (HD group) in the dorsal region, then, AST1 may represent a more stable and aging-driven astrocytic phenotype, with limited sensitivity to masticatory modulation during advanced aging. Therefore, in AST2 of HD group, aged animals exhibited greater complexity compared to young animals, suggesting the occurrence of adaptive or compensatory astroglial remodeling during physiological aging. Behavioral analysis showed an age-dependent reduction in learning performance in the HD group, where 18 M mice exhibited a significantly lower contrast index than 6 M old mice on day 4 of the Morris Water Maze task. These findings highlight that morphological changes in astrocytes within the dorsal SLM may contribute to age-related alterations in hippocampus-dependent learning. Overall, maintaining proper mastication may be an effective approach to maintain astrocytic integrity during aging and preserve hippocampus-dependent cognitive function, particularly in older individuals.