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

Area of Science:

• Neuroscience
• Cognitive Science
• Aging Research

Background:

• Alzheimer's disease (AD) involves progressive cognitive decline.
• Cognitive reserve can mitigate AD's effects.
• Investigating early cognitive stimulation's impact on brain function is crucial.

Purpose of the Study:

• To determine if long-term cognitive stimulation preserves brain function in male and female TgF344-AD rats before amyloid deposition.
• To explore sex-specific differences in response to cognitive training.

Main Methods:

• TgF344-AD and wild-type (WT) rats received cognitive training or remained untrained.
• Resting-state fMRI, novel object recognition tests, and molecular analyses were employed.
• Evaluated functional connectivity, memory, synaptic plasticity, inhibitory signaling, and microglial reactivity.

Main Results:

• Females exhibited higher baseline task engagement and synaptic protein levels than males.
• Cognitive training enhanced connectivity and memory in males, with minor benefits in females.
• Trained transgenic rats maintained entorhinal-hippocampal connectivity; males showed sustained plasticity and reduced parvalbumin-positive interneurons.
• Early training promoted microglial recruitment and reduced reactivity to plaques.

Conclusions:

• Early and sustained cognitive stimulation enhances brain resilience in the context of AD.
• Sex-specific mechanisms significantly influence the outcomes of cognitive interventions.
• Cognitive training offers potential benefits for mitigating AD-related brain changes, particularly in males.