Early-life cognitive intervention preserves brain function in aged TgF344-AD rats with sex-specific effects

Alzheimer’s disease is characterized by progressive cognitive decline, and its effects are mitigated by cognitivereserve. We investigated whether long-term cognitive stimulation, initiated before amyloid deposition,preserves brain function in male and female TgF344-AD rats. Transgenic and wild-type...

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Detalles Bibliográficos
Autores: Molina Porcel, Laura, Malagelada Grau, Cristina, Soria, Guadalupe, Casanova-Pagola, Julia, Varriano, Federico, López-Gil, Xavier, Campoy Campos, Genís, Abellí Deulofeu, Enric, García-González, Clara, López-Bravo, Elisa, Tudela Fernández, Raúl, Muñoz-Moreno, Emma, Aguado Tomàs, Fernando, Prats Galino, Alberto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/226531
Acceso en línea:https://hdl.handle.net/2445/226531
Access Level:acceso abierto
Palabra clave:Malaltia d'Alzheimer
Neurociència cognitiva
Alzheimer's disease
Cognitive neuroscience
Descripción
Sumario:Alzheimer’s disease is characterized by progressive cognitive decline, and its effects are mitigated by cognitivereserve. We investigated whether long-term cognitive stimulation, initiated before amyloid deposition,preserves brain function in male and female TgF344-AD rats. Transgenic and wild-type (WT) rats underwentcognitive training or remained untrained. Resting-state fMRI assessed functional connectivity, the novel objectrecognition test evaluated memory, and molecular analyses examined synaptic plasticity, inhibitorysignaling, and microglial reactivity. At baseline, females showed greater task engagement and higher synapticprotein levels (PSD95, TrkB, and VGLUT) than males. Cognitive training improved connectivity and memoryin males, with limited benefits in females. At 19 months, trained transgenic rats maintained entorhinal-hippocampalconnectivity resembling WT rats, with males showing sustained plasticity markers and reducedparvalbumin-positive interneurons. Trained 11-month-old rats showed enhanced microglial recruitment toplaques and a less reactive phenotype. Overall, early and sustained cognitive stimulation enhances brain resilience,with sex-specific mechanisms shaping outcomes.

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